268 results on '"Hongchen Gu"'
Search Results
2. MSU crystal deposition contributes to inflammation and immune responses in gout remission
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Hongchen Gu, Hanqing Yu, Ling Qin, Hanjie Yu, Yaxiang Song, Guangqi Chen, Dake Zhao, Shu Wang, Wen Xue, Ling Wang, Zisheng Ai, Bei Xu, and Ai Peng
- Subjects
CP: Immunology ,Biology (General) ,QH301-705.5 - Abstract
Summary: As a prominent feature of gout, monosodium urate (MSU) crystal deposition induces gout flares, but its impact on immune inflammation in gout remission remains unclear. Using single-cell RNA sequencing (scRNA-seq), we characterize the transcription profiling of peripheral blood mononuclear cells (PBMCs) among intercritical remission gout, advanced remission gout, and normal controls. We find systemic inflammation in gout remission with MSU crystal deposition at the intercritical and advanced stages, evidenced by activated inflammatory pathways, strengthened inflammatory cell-cell interactions, and elevated arachidonic acid metabolic activity. We also find increased HLA-DQA1high classic monocytes and PTGS2high monocytes in advanced gout and overactivated CD8+ T cell subtypes in intercritical and advanced gout. Additionally, the osteoclast differentiation pathway is significantly enriched in monocytes, T cells, and B cells from advanced gout. Overall, we demonstrate systemic inflammation and distinctive immune responses in gout remission with MSU crystal deposition, allowing further exploration of the underlying mechanism and clinical significance in conversion from intercritical to advanced stage.
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- 2023
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3. Emerging advances in nanobiomaterials-assisted chimeric antigen receptor (CAR)-macrophages for tumor immunotherapy
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Yanan Zhang, Jingxing Yang, Tinghao Zhang, and Hongchen Gu
- Subjects
cancer immunotherapy ,nanobiomaterials ,chimeric antigen receptor ,tumor-associated macrophages (TAMs) ,genetic engineering ,Biotechnology ,TP248.13-248.65 - Abstract
Adoptive cell immunotherapy, especially chimeric antigen receptor (CAR)-T-cells therapy, has made great progress in the clinical treatment of hematological malignancies. However, restricted by the complex tumor microenvironment, the potential efficiency of T-cell infiltration and activated immune cells are limited, thus failure prevented the progression of the solid tumor. Alternatively, tumor-associated macrophages (TAMs), one sustentacular and heterogeneous cellular population within the tumor microenvironment, are regarded as potential therapeutic targets. Recently, CARs have shown tremendous promise in treating malignancies by equipping macrophages. This novel therapeutic strategy circumvents the tumor microenvironment’s limitations and provides a safer therapeutic approach. Meanwhile, nanobiomaterials as gene delivery carriers not only substantially reduce the treatment cost of this novel therapeutic strategy, but also set the foundation for in vivo CAR-M therapy. Here, we highlight the major strategies prepared for CAR-M, emphasizing the challenges and opportunities of these approaches. First, the common therapeutic strategies for macrophages are summarized in clinical and preclinical trials. Namely, TAM-targeted therapeutic strategies: 1) Inhibit monocyte or macrophage recruitment into tumors, 2) deplete TAMs, and 3) reprogramme TAMs to antitumor M1 phenotype. Second, the current development and progress of CAR-M therapy are reviewed, including the researchers’ attempts in CAR structure design, cell origin, and gene delivery vectors, especially nanobiomaterials as an alternative to viral vectors, as well as some challenges faced by current CAR-M therapy are also summarized and discussed. Finally, the field of genetically engineered macrophages integration with nanotechnology for the future in oncology has been prospected.
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- 2023
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4. Programmable design of isothermal nucleic acid diagnostic assays through abstraction-based models
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Gaolian Xu, Julien Reboud, Yunfei Guo, Hao Yang, Hongchen Gu, Chunhai Fan, Xiaohua Qian, and Jonathan M. Cooper
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Science - Abstract
Detecting nucleic acids often requires choosing between different amplification mechanisms. Here the authors present a generalisable and programmable isothermal methodology, demonstrated in clinical applications, including for multiplexed detection of short miRNAs.
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- 2022
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5. Evolution of 'On-Barcode' Luminescence Oxygen Channeling Immunoassay by Exploring the Barcode Structure and the Assay System
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Zuying Feng, Qingsheng Guo, Yao Wang, Yunfei Ge, Zhiying Zhang, Yan Wu, Qilong Li, Hajar Masoomi, Hongchen Gu, and Hong Xu
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Chemistry ,QD1-999 - Published
- 2022
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6. Author Correction: Sequence terminus dependent PCR for site-specific mutation and modification detection
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Gaolian Xu, Hao Yang, Jiani Qiu, Julien Reboud, Linqing Zhen, Wei Ren, Hong Xu, Jonathan M. Cooper, and Hongchen Gu
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Science - Published
- 2023
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7. Plasma biomarker profiles and the correlation with cognitive function across the clinical spectrum of Alzheimer’s disease
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Zhenxu Xiao, Xue Wu, Wanqing Wu, Jingwei Yi, Xiaoniu Liang, Saineng Ding, Li Zheng, Jianfeng Luo, Hongchen Gu, Qianhua Zhao, Hong Xu, and Ding Ding
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Plasma p-tau181 ,Simoa ,Cognitive domain ,CDR ,Alzheimer’s disease ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Plasma biomarkers showed a promising value in the disease diagnosis and management of Alzheimer’s disease (AD). However, profiles of the biomarkers and the associations with cognition across a spectrum of cognitive stages have seldom been reported. Methods We recruited 320 individuals with cognitive impairment and 131 cognitively normal participants from a memory clinic and a community cohort. Participants were classified into 6 groups based on their Clinical Dementia Rating (CDR) scores and clinical diagnosis, including AD, amnestic mild cognitive impairment (aMCI), and normal cognition (NC). A battery of neuropsychological tests was used to assess the global and domain-specific cognition. Plasma Aβ1-40, Aβ1-42, Aβ1-42/Aβ1-40, total tau (t-tau), neurofilament protein light chain (NfL), and phosphorylated tau at threonine 181 (p-tau181) were quantified using the single-molecule array (Simoa) platform. Results All the plasma markers (Aβ1-40, Aβ1-42, Aβ1-42/Aβ1-40, t-tau, NfL, p-tau181) showed certain discrepancies among NC, aMCI, and AD groups. The p-tau181 level showed a continuous escalating trend as the CDR scores increased from 0 (NC group) to 3 (severe AD). Compared with other biomarkers, p-tau181 had correlations with broader cognitive domains, covering global cognition (r = −0.536, P < 0.0001), memory (r = −0.481, P < 0.0001), attention (r = −0.437, P < 0.0001), visuospatial function (r = −0.385, P < 0.0001), and language (r = −0.177, P = 0.0003). Among participants with CDR ≥ 1, higher p-tau181 was correlated with worse global cognition (r = −0.301, P < 0.001). Conclusions Plasma p-tau181 had correlations with broader cognitive domains, suggesting its potential as a promising clinical-relevant blood-based biomarker.
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- 2021
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8. Osteogenic and antibacterial dual functions of a novel levofloxacin loaded mesoporous silica microspheres/nano-hydroxyapatite/polyurethane composite scaffold
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Zhiping Kuang, Guangming Dai, Ruijie Wan, Dongli Zhang, Chen Zhao, Cheng Chen, Jidong Li, Hongchen Gu, and Wei Huang
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Antibacterial ,Composite scaffold ,Levofloxacin ,Nanobiomaterial ,Osteogenesis ,Medicine (General) ,R5-920 ,Genetics ,QH426-470 - Abstract
Lev/MSNs/n-HA/PU has been proved to be a novel scaffold material to treat bone defect caused by chronic osteomyelitis. We have previously identified that this material can effectively treat chronic osteomyelitis caused by Staphylococcus aureus in vivo. However, the potential mechanisms of antibacterial and osteogenic induction properties remain unclear. Thus, for osteogenesis property, immunohistochemistry, PCR, and Western blot were performed to detect the expression of osteogenic markers. Furthermore, flow cytometry and TUNEL were applied to analyze MC3T3-E1 proliferation and apoptosis. For antibacterial property, the material was co-cultivated with bacteria, bacterial colony forming units was counted and the release time of the effective levofloxacin was assayed by agar disc-diffusion test. Moreover, scanning electron microscope was applied to observe adhesion of bacteria. In terms of osteogenic induction, we found BMSCs adherently grew more prominently on Lev/MSNs/n-HA/PU. Lev/MSNs/n-HA/PU also enhanced the expression of osteogenic markers including OCN and COL1α1, as well as effectively promoted the transition from G1 phase to G2 phase. Furthermore, Lev/MSNs/n-HA/PU could reduce apoptosis of MC3T3-E1. Besides, both Lev/MSNs/n-HA/PU and n-HA/PU materials could inhibit bacterial colonies, while Lev/MSNs/n-HA/PU possessed a stronger antibacterial activities, and lower bacterial adhesion than n-HA/PU. These results illustrated that Lev/MSNs/n-HA/PU composite scaffold possess favorable compatibility in vitro, which induce osteogenic differentiation of MSCs, promote proliferation and differentiation of MC3T3-E1, and inhibit apoptosis. Moreover, clear in vitro antibacterial effect of Lev/MSNs/n-HA/PU was also observed. In summary, this study replenishes the potential of Lev/MSNs/n-HA/PU composite scaffold possess dual functions of anti-infection and enhanced osteogenesis for future clinical application.
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- 2021
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9. Mannose and Hyaluronic Acid Dual-Modified Iron Oxide Enhances Neoantigen-Based Peptide Vaccine Therapy by Polarizing Tumor-Associated Macrophages
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Ying Nie, Lu Shi, Yanan Zhang, Yunfei Guo, and Hongchen Gu
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macrophage polarization ,iron oxide ,mannose ,hyaluronic acid ,tumor-associated macrophages ,cancer vaccine ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Neoantigen-based cancer vaccine therapy is a breakthrough in the field of immunotherapy. However, it is difficult for vaccines against neoantigens to overcome the immunosuppressive microenvironment, where tumor-associated macrophages (TAMs) play a significant role. Herein, we report an iron oxide nanoparticle modified with hyaluronic acid and mannose to reshape the tumor microenvironment by targeting and repolarizing TAMs from protumor M2 to antitumor M1 phenotype. Mannose decoration could confer the nanoparticle-enhanced TAM targeting ability, while hyaluronic acid and iron oxide could repolarize M2-like macrophages both in vitro and in vivo. Combined with antigenic peptides, this nanovaccine could significantly increase the infiltration of CD8+ T cells into tumor tissue and strongly activate dendritic cells in sentinel lymph nodes. Finally, we used the dual-modified nanoparticles to first convert the tumor microenvironment and then the nanovaccine administration in a TC1 tumor model to further enhance efficacy. This strategy inhibited tumor growth and achieved a 40% cure rate in mice (two of five). In summary, this study provides a potent and rationally designed nanoadjuvant to enhance antitumor efficiency and facilitate delivery of neoantigen vaccines by repolarizing TAMs and harmonizing immune cells.
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- 2022
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10. Determination of the Binding Constant between Oligonucleotide-Coupled Magnetic Microspheres and Target DNA
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Mengting Zhou, Xiaomin Chen, Hao Yang, Xiaoxia Fang, Hongchen Gu, and Hong Xu
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Chemistry ,QD1-999 - Published
- 2019
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11. Emerging Nanoparticle Strategies for Modulating Tumor-Associated Macrophage Polarization
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Lu Shi and Hongchen Gu
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macrophage polarization ,tumor-associated macrophages ,nanoparticles ,drug delivery ,tumor microenvironment ,cancer immunotherapy ,Microbiology ,QR1-502 - Abstract
Immunotherapy has made great progress in recent years, yet the efficacy of solid tumors remains far less than expected. One of the main hurdles is to overcome the immune-suppressive tumor microenvironment (TME). Among all cells in TME, tumor-associated macrophages (TAMs) play pivotal roles because of their abundance, multifaceted interactions to adaptive and host immune systems, as well as their context-dependent plasticity. Underlying the highly plastic characteristic, lots of research interests are focused on repolarizing TAMs from M2-like pro-tumor phenotype towards M1-like antitumoral ones. Nanotechnology offers great opportunities for targeting and modulating TAM polarization to mount the therapeutic efficacy in cancer immunotherapy. Here, this mini-review highlights those emerging nano-approaches for TAM repolarization in the last three years.
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- 2021
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12. NAD⁺-carrying mesoporous silica nanoparticles can prevent oxidative stress-induced energy failures of both rodent astrocytes and PC12 cells.
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Heyu Chen, Yao Wang, Jixi Zhang, Yingxin Ma, Caixia Wang, Ying Zhou, Hongchen Gu, and Weihai Ying
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Medicine ,Science - Abstract
AIM: To test the hypothesis that NAD(+)-carrying mesoporous silica nanoparticles (M-MSNs@NAD+) can effectively deliver NAD(+) into cells to produce cytoprotective effects. METHODS & MATERIALS: NAD(+) was incorporated into M-MSNs. Primary rat astrocyte cultures and PC12 cells were treated with H₂O₂, followed by post-treatment with M-MSNs@NAD+. After various durations of the post-treatment, intracellular NAD(+) levels, intracellular ATP levels and lactate dehydrogenase (LDH) release were determined. RESULTS & DISCUSSION: M-MSNs can be effectively loaded with NAD(+). The M-MSNs@NAD+ can significantly attenuate H₂O₂-induced NAD(+) and ATP decreases in both astrocyte cultures and PC12 cells. M-MSNs@NAD+ can also partially prevent the H₂O₂-induced LDH release from both astrocyte cultures and PC12 cells. In contrast, the NAD(+) that is spontaneously released from the M-MSNs@NAD+ is insufficient to prevent the H₂O₂-induced damage. CONCLUSIONS: Our study has suggested the first approach that can effectively deliver NAD(+) into cells, which provides an important basis both for elucidating the roles of intracellular NAD(+) in biological functions and for therapeutic applications of NAD(+). Our study has also provided the first direct evidence demonstrating a key role of NAD(+) depletion in oxidative stress-induced ATP decreases.
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- 2013
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13. Bead-Based Multiplexed Droplet Digital Polymerase Chain Reaction in a Single Tube Using Universal Sequences: An Ultrasensitive, Cross-Reaction-Free, and High-Throughput Strategy
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Zhejia Gu, Tong Sun, Qingsheng Guo, Yao Wang, Yunfei Ge, Hongchen Gu, Gaolian Xu, and Hong Xu
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Fluid Flow and Transfer Processes ,COVID-19 Testing ,SARS-CoV-2 ,Process Chemistry and Technology ,Aluminum Oxide ,Biotin ,COVID-19 ,Humans ,Bioengineering ,Streptavidin ,Multiplex Polymerase Chain Reaction ,Instrumentation ,Fluorescent Dyes - Abstract
The multiplexed digital polymerase chain reaction (PCR) is widely used in molecular diagnosis owing to its high sensitivity and throughput for multiple target detection compared with the single-plexed digital PCR; however, current multiplexed digital PCR technologies lack efficient coding strategies that do not compromise the sensitivity and signal-to-noise (
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- 2022
14. A micro-chamber free digital bio-detection for multiplexed and ultrasensitive immunoassay based on encoded magnetic microbeads and tyramide signal amplification strategy
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Jiayu Zhang, Jiancong Wu, Cang Chen, Guoqing He, Wei Liu, Sitong Xu, Hongchen Gu, Yao Wang, and Hong Xu
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Analytical Chemistry - Published
- 2023
15. Cell membrane-camouflaged liposomes and neopeptide-loaded liposomes with TLR agonist R848 provides a prime and boost strategy for efficient personalized cancer vaccine therapy
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Lu Shi and Hongchen Gu
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History ,Polymers and Plastics ,Biomedical Engineering ,Pharmaceutical Science ,Molecular Medicine ,Medicine (miscellaneous) ,General Materials Science ,Bioengineering ,Business and International Management ,Industrial and Manufacturing Engineering - Abstract
Recent advances in bioinformatics and nanotechnology offer great opportunities for personalized cancer vaccine development. However, the timely identification of neoantigens and unsatisfactory efficacy of therapeutic cancer vaccines remain two obstacles for clinical transformation. We propose a "prime and boost" strategy to facilitate neoantigen-based immunotherapy. To prime the immune system, we first constructed personalized liposomes with cancer cell membranes and adjuvant R848 to provide immunostimulatory efficacy and time for identifying tumor antigens. Liposomes loaded with personalized neopeptides and adjuvants were used to boost the immune response. In vitro experiments verified potent immune responses, including macrophage polarization, dendritic cell maturation, and T lymphocyte activation. In vivo B16F10 and TC-1 cancer model were used to investigate efficient tumor growth suppression. Liposomal vaccines with neopeptides could stimulate human dendritic cells and T lymphocytes in vitro. These results demonstrate that the "prime and boost" strategy provides simple, quick, and efficient personalized vaccines for cancer therapy.
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- 2022
16. A magnetic bead-mediated selective adsorption strategy for extracellular vesicle separation and purification
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Cang Chen, Xiaoxia Fang, Bing Liu, Fenglin Hu, Hong Xu, Zhijie Ma, Hongchen Gu, and Haiyan Li
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0206 medical engineering ,Biomedical Engineering ,Magnetic separation ,02 engineering and technology ,Biochemistry ,Extracellular vesicles ,Microsphere ,Biomaterials ,Extracellular Vesicles ,Molecular Biology ,Chromatography ,Chemistry ,Magnetic Phenomena ,General Medicine ,Extracellular vesicle ,021001 nanoscience & nanotechnology ,020601 biomedical engineering ,MicroRNAs ,Yield (chemistry) ,Magnetic bead ,Selective adsorption ,Separation method ,Adsorption ,0210 nano-technology ,Ultracentrifugation ,Biotechnology - Abstract
Extracellular vesicles (EVs) are membrane-encapsulated particles with critical biomedical functions, including mediating intercellular communication, assisting tumor metastasis, and carrying protein and microRNA biomarkers. The downstream applications of EVs are greatly influenced by the quality of the isolated EVs. However, almost none of the separation methods can simultaneously achieve both high yield and high purity of the isolated EVs, thus making the isolation of EVs an essential challenge in EV research. Here, we developed a magnetic bead-mediated selective adsorption strategy (MagExo) for easy-to-operate EV isolation. Benefited from the presence of an adsorption window between EVs and proteins under the effect of a hydrophilic polymer, EVs tend to adsorb on the surface of magnetic beads selectively and can be separated from biological fluids with high purity by simple magnetic separation. The proposed method was used for EV isolation from plasma and cell culture media (CCM), with two times higher yield and comparable purity of the harvested EVs to that obtained by ultracentrifugation (UC). Downstream applications in proteomics analysis showed 86.6% (plasma) and 86.5% (CCM) of the analyzed proteins were matched with the ExoCarta database, which indicates MagExo indeed enriches EVs efficiently. Furthermore, we found the target RNA amount of the isolated EVs by MagExo were almost dozens and hundred times higher than the gold standard DG-UC and ultracentrifugation (UC) methods, respectively. All the results show that MagExo is a reliable, easy, and efficient approach to harvest EVs for a wide variety of downstream applications with minimized sample usage. STATEMENT OF SIGNIFICANCE: Extracellular vesicles (EVs) are presently attracting increasing interest among clinical and scientific researchers. Although the downstream applications of EVs are recognized to be greatly affected by the quality of the isolated EVs, almost none of the separation methods can simultaneously achieve high yield and high purity of the isolated EVs; this makes the isolation of EVs an essential challenge in EV research. In the present work, we proposed a simple and easy-to-operate method (MagExo) for the separation and purification of EVs based on the phenomenon that EVs can be selectively adsorbed on the surface of magnetic microspheres in the presence of a hydrophilic polymer. The performance of MagExo was comparable to or even better than that of gold standard methods and commercial kits, with two times higher yield and comparable purity of the harvested EVs to that achieved with ultracentrifugation (UC); this could meet the requirements of various EV-associated downstream applications. In addition, MagExo can be easily automated by commercial liquid workstations, thus significantly improving the isolation throughput and paving a new way in clinical diagnosis and treatment.
- Published
- 2021
17. Osteogenic and antibacterial dual functions of a novel levofloxacin loaded mesoporous silica microspheres/nano-hydroxyapatite/polyurethane composite scaffold
- Author
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Chen Zhao, Zhi‐ping Kuang, Wei Huang, Dai Guangming, Rui‐jie Wan, Hongchen Gu, Jidong Li, Cheng Cheng Chen, and Dongli Zhang
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Medicine (General) ,Levofloxacin ,02 engineering and technology ,QH426-470 ,010402 general chemistry ,medicine.disease_cause ,01 natural sciences ,Biochemistry ,Flow cytometry ,R5-920 ,Western blot ,Osteogenesis ,Full Length Article ,Genetics ,medicine ,Molecular Biology ,Genetics (clinical) ,Nanobiomaterial ,Composite scaffold ,biology ,medicine.diagnostic_test ,Chemistry ,Mesenchymal stem cell ,Cell Biology ,Adhesion ,Mesoporous silica ,021001 nanoscience & nanotechnology ,biology.organism_classification ,Molecular biology ,0104 chemical sciences ,Antibacterial ,Apoptosis ,Staphylococcus aureus ,0210 nano-technology ,Bacteria - Abstract
Lev/MSNs/n-HA/PU has been proved to be a novel scaffold material to treat bone defect caused by chronic osteomyelitis. We have previously identified that this material can effectively treat chronic osteomyelitis caused by Staphylococcus aureus in vivo. However, the potential mechanisms of antibacterial and osteogenic induction properties remain unclear. Thus, for osteogenesis property, immunohistochemistry, PCR, and Western blot were performed to detect the expression of osteogenic markers. Furthermore, flow cytometry and TUNEL were applied to analyze MC3T3-E1 proliferation and apoptosis. For antibacterial property, the material was co-cultivated with bacteria, bacterial colony forming units was counted and the release time of the effective levofloxacin was assayed by agar disc-diffusion test. Moreover, scanning electron microscope was applied to observe adhesion of bacteria. In terms of osteogenic induction, we found BMSCs adherently grew more prominently on Lev/MSNs/n-HA/PU. Lev/MSNs/n-HA/PU also enhanced the expression of osteogenic markers including OCN and COL1α1, as well as effectively promoted the transition from G1 phase to G2 phase. Furthermore, Lev/MSNs/n-HA/PU could reduce apoptosis of MC3T3-E1. Besides, both Lev/MSNs/n-HA/PU and n-HA/PU materials could inhibit bacterial colonies, while Lev/MSNs/n-HA/PU possessed a stronger antibacterial activities, and lower bacterial adhesion than n-HA/PU. These results illustrated that Lev/MSNs/n-HA/PU composite scaffold possess favorable compatibility in vitro, which induce osteogenic differentiation of MSCs, promote proliferation and differentiation of MC3T3-E1, and inhibit apoptosis. Moreover, clear in vitro antibacterial effect of Lev/MSNs/n-HA/PU was also observed. In summary, this study replenishes the potential of Lev/MSNs/n-HA/PU composite scaffold possess dual functions of anti-infection and enhanced osteogenesis for future clinical application.
- Published
- 2021
18. Ultrasensitive monitoring of SARS-CoV-2-specific antibody responses based on a digital approach reveals one week of IgG seroconversion
- Author
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Feiyang Ou, Danyun Lai, Xiaojun Kuang, Ping He, Yang Li, He-wei Jiang, Wei Liu, Hongping Wei, Hongchen Gu, Yuan qiao Ji, Hong Xu, and Sheng-ce Tao
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Vaccines ,SARS-CoV-2 ,Biomedical Engineering ,Biophysics ,COVID-19 ,General Medicine ,Biosensing Techniques ,Antibodies, Viral ,Sensitivity and Specificity ,Immunoglobulin M ,Seroconversion ,Immunoglobulin G ,Nucleic Acids ,Antibody Formation ,Electrochemistry ,Humans ,Biotechnology - Abstract
COVID-19 is still unfolding, while many people have been vaccinated. In comparison to nucleic acid testing (NAT), antibody-based immunoassays are faster and more convenient. However, its application has been hampered by its lower sensitivity and the existing fact that by traditional immunoassays, the measurable seroconversion time of pathogen-specific antibodies, such as IgM or IgG, lags far behind that of nucleic acids. Herein, by combining the single molecule array platform (Simoa), RBD, and a previously identified SARS-CoV-2 S2 protein derivatized 12-aa peptide (S2-78), we developed and optimized an ultrasensitive assay (UIM-COVID-19 assay). Sera collected from three sources were tested, i.e., convalescents, inactivated virus vaccine-immunized donors and wild-type authentic SARS-CoV-2-infected rhesus monkeys. The sensitivities of UIM-COVID-19 assays are 100-10,000 times higher than those of conventional flow cytometry, which is a relatively sensitive detection method at present. For the established UIM-COVID-19 assay using RBD as a probe, the IgG and IgM seroconversion times after vaccination were 7.5 and 8.6 days vs. 21.4 and 24 days for the flow cytometry assay, respectively. In addition, using S2-78 as a probe, the UIM-COVID-19 assay could differentiate COVID-19 patients (convalescents) from healthy people and patients with other diseases, with AUCs ranging from 0.85-0.95. In summary, the UIM-COVID-19 we developed here is a promising ultrasensitive biodetection strategy that has the potential to be applied for both immunological studies and diagnostics.
- Published
- 2022
19. Sensitive GlaI digestion and terminal transferase PCR for DNA methylation detection
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Hao Yang, Jiani Qiu, LinQing Zhen, Yizhou Huang, Wei Ren, Hongchen Gu, Hong Xu, and Gaolian Xu
- Subjects
DNA Nucleotidylexotransferase ,Digestion ,DNA ,DNA Methylation ,Polymerase Chain Reaction ,Analytical Chemistry - Abstract
Highly sensitive and specific detection of DNA methylation is critical for early diagnosis and therapy of cancer. Herein, we propose a novel bisulfite-free PCR assay based on a GlaI methylation specific digestion and terminal transferase (TdT) extension for the detection of methylated DNA with high sensitivity and specificity, denoted as GlaI-TdT methylation PCR. For GlaI-TdT methylation PCR assay, the methylated CpG site is recognized and cut by GlaI selectively firstly, leading to the generation of product with specific free 3' end. The free 3' end can be further extended with TdT and served as template for the followed quantitative PCR. The specificity of GlaI-TdT methylation PCR depends on the specific methylation discrimination of GlaI and the existence of poly-T sequence as the extension of TdT. The sensitivity of GlaI-TdT PCR for methylated DNA can achieve 10 copies/reaction with 10,000 copies unmethylated background. The detection performance of GlaI-TdT methylation PCR was also evaluated using colorectal cancer tissue samples, with the results shown great accordance with standard bisulfite-PCR sequencing. Based on its high sensitivity, high specificity, simple and convenient, GlaI-TdT methylation PCR has the great potential to become a promising and robust bisulfite-free procedure for the detection of DNA methylations.
- Published
- 2022
20. Multiplexed Digital Enzyme-Linked Immunoassay Based on Enzyme Signal Amplification in Microdroplets: A Universal, Practical, Multiplexed Ultrasensitive Biodetection Platform
- Author
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Jingwei Yi, Zehang Gao, Qingsheng Guo, You Wu, Tong Sun, Yao Wang, Hongbo Zhou, Hongchen Gu, Jianlong Zhao, and Hong Xu
- Subjects
History ,Polymers and Plastics ,Business and International Management ,Industrial and Manufacturing Engineering - Published
- 2022
21. Silver nanoparticles-decorated and mesoporous silica coated single-walled carbon nanotubes with an enhanced antibacterial activity for killing drug-resistant bacteria
- Author
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Yao Wang, Hongchen Gu, Yanmao Wang, Yimin Chai, Jia Xu, Cang Chen, and Yu Zhu
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Biocompatibility ,Chemistry ,02 engineering and technology ,Carbon nanotube ,Mesoporous silica ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,01 natural sciences ,Atomic and Molecular Physics, and Optics ,Silver nanoparticle ,Bacterial cell structure ,0104 chemical sciences ,law.invention ,Membrane ,Chemical engineering ,law ,General Materials Science ,Electrical and Electronic Engineering ,0210 nano-technology ,Mesoporous material ,Antibacterial activity - Abstract
The mounting threat of antibiotic-resistant bacterial infections has made it imperative to develop innovative antibacterial strategies. Here we propose a novel antibacterial nanoplatform of silver nanoparticles-decorated and mesoporous silica coated single-walled carbon nanotubes constructed via a N-[3-(trimethoxysilyl)propyl]ethylene diamine (TSD)-mediated method (SWCNTs@mSiO2-TSD@Ag). In this system, the outer mesoporous silica shells are able to improve the dispersibility of SWCNTs, which will increase their contact area with bacteria cell walls. Meanwhile, the large number of mesopores in silica layers act as microreactors for in situ synthesis of Ag NPs with controlled small size and uniform distribution, which induces an enhanced antibacterial activity. Compared with TSD modified mesoporous silica coated single-walled carbon nanotubes (SWCNTs@mSiO2-TSD) and commercial Ag NPs, this combination nanosystem of SWCNTs@mSiO2-TSD@Ag exhibits much stronger antibacterial performance against multi-drug-resistant bacteria Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) in vitro through damaging the bacterial cell membranes and a fast release of silver ions. Furthermore, the in vivo rat skin infection model verifies that SWCNTs@mSiO2-TSD@Ag have remarkably improved abilities of bacterial clearance, wound healing promoting as well as outstanding biocompatibility. Therefore, this novel nanoplatform indicates promising potentials as a safe and powerful tool for the treatment of clinical drug-resistant infections.
- Published
- 2020
22. Multiplexed digital ELISA in picoliter droplets based on enzyme signal amplification block and precisely decoding strategy: A universal and practical biodetection platform
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Jingwei Yi, Zehang Gao, Qingsheng Guo, You Wu, Tong Sun, Yao Wang, Hongbo Zhou, Hongchen Gu, Jianlong Zhao, and Hong Xu
- Subjects
Materials Chemistry ,Metals and Alloys ,Electrical and Electronic Engineering ,Condensed Matter Physics ,Instrumentation ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials - Published
- 2022
23. Breaking through the Poisson Distribution: A compact high-efficiency droplet microfluidic system for single-bead encapsulation and digital immunoassay detection
- Author
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Xiaoyu Yue, Xiaoxia Fang, Tong Sun, Jingwei Yi, Xiaojun Kuang, Qingsheng Guo, Yao Wang, Hongchen Gu, and Hong Xu
- Subjects
Immunoassay ,Microfluidics ,Electrochemistry ,Biomedical Engineering ,Biophysics ,Biosensing Techniques ,Poisson Distribution ,General Medicine ,Microfluidic Analytical Techniques ,Single-Cell Analysis ,Biotechnology - Abstract
Droplet encapsulation of a single cell or bead is widely used in digital detection, single-cell sequencing, and drug screening. However, the encapsulation of particles is totally random restricted by the Poisson distribution. The theoretical possibility of single-particle encapsulation is usually only approximately 10%. In ultra-high multiplexed digital detection or other applications that needing to measure large numbers of particles, the number of the partitions required to be counted is extremely high, further result in great increase of statistical number of invalid droplets and the redundancy of detection data. Here, a bead ordered arrangement droplet (BOAD) system is proposed to break through the Poisson distribution. BOAD system tactfully combines sheath flow, Dean vortex, and compression flow channel to achieve orderly arrangement of particles for the first time, and could achieve the fastest orderly arrangement of particles in the shortest structure. The efficiency of single-bead encapsulation is improved to as high as 86%. Further application to encapsulate encoding beads and IL-10-targeted magnetic beads demonstrates the potential for bead-based ultra-high multiplexed digital detection. Thus, use of the BOAD system is very promising for many applications needing high single-particle encapsulation ratio in limited partitions, such as multiplexed digital bio-detection, single-cell analysis, drug screening, and single exosome detection.
- Published
- 2022
24. Plasma biomarker profiles and the correlation with cognitive function across the clinical spectrum of Alzheimer’s disease
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Jingwei Yi, Ding Ding, Zhenxu Xiao, Hong Xu, Xue Wu, Qianhua Zhao, Hongchen Gu, Saineng Ding, Xiaoniu Liang, Jianfeng Luo, Wanqing Wu, and Li Zheng
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,Neurology ,Clinical Dementia Rating ,Cognitive Neuroscience ,Neurosciences. Biological psychiatry. Neuropsychiatry ,tau Proteins ,Neuropsychological Tests ,CDR ,Correlation ,Simoa ,03 medical and health sciences ,Cognition ,0302 clinical medicine ,Alzheimer Disease ,Internal medicine ,Plasma p-tau181 ,Humans ,Medicine ,Cognitive Dysfunction ,Cognitive domain ,Effects of sleep deprivation on cognitive performance ,RC346-429 ,Beta (finance) ,Amyloid beta-Peptides ,business.industry ,Research ,Memory clinic ,Neuropsychology ,medicine.disease ,030104 developmental biology ,Cohort ,Biomarker (medicine) ,Neurology. Diseases of the nervous system ,Neurology (clinical) ,Alzheimer's disease ,business ,Alzheimer’s disease ,Biomarkers ,030217 neurology & neurosurgery ,RC321-571 - Abstract
Background Plasma biomarkers showed a promising value in the disease diagnosis and management of Alzheimer’s disease (AD). However, profiles of the biomarkers and the associations with cognition across a spectrum of cognitive stages have seldom been reported. Methods We recruited 320 individuals with cognitive impairment and 131 cognitively normal participants from a memory clinic and a community cohort. Participants were classified into 6 groups based on their Clinical Dementia Rating (CDR) scores and clinical diagnosis, including AD, amnestic mild cognitive impairment (aMCI), and normal cognition (NC). A battery of neuropsychological tests was used to assess the global and domain-specific cognition. Plasma Aβ1-40, Aβ1-42, Aβ1-42/Aβ1-40, total tau (t-tau), neurofilament protein light chain (NfL), and phosphorylated tau at threonine 181 (p-tau181) were quantified using the single-molecule array (Simoa) platform. Results All the plasma markers (Aβ1-40, Aβ1-42, Aβ1-42/Aβ1-40, t-tau, NfL, p-tau181) showed certain discrepancies among NC, aMCI, and AD groups. The p-tau181 level showed a continuous escalating trend as the CDR scores increased from 0 (NC group) to 3 (severe AD). Compared with other biomarkers, p-tau181 had correlations with broader cognitive domains, covering global cognition (r = −0.536, P < 0.0001), memory (r = −0.481, P < 0.0001), attention (r = −0.437, P < 0.0001), visuospatial function (r = −0.385, P < 0.0001), and language (r = −0.177, P = 0.0003). Among participants with CDR ≥ 1, higher p-tau181 was correlated with worse global cognition (r = −0.301, P < 0.001). Conclusions Plasma p-tau181 had correlations with broader cognitive domains, suggesting its potential as a promising clinical-relevant blood-based biomarker.
- Published
- 2021
25. Development of a Plasma Biomarker Diagnostic Model Incorporating Ultrasensitive Digital Immunoassay as a Screening Strategy for Alzheimer Disease in a Chinese Population
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Hongchen Gu, Jingwei Yi, Ding Ding, Li Zheng, Xue Wu, Qianhua Zhao, Jianfeng Luo, Zhenxu Xiao, Wanqing Wu, Saineng Ding, Hong Xu, and Xiaoniu Liang
- Subjects
Oncology ,Immunoassay ,medicine.medical_specialty ,Chinese population ,China ,Amyloid beta-Peptides ,medicine.diagnostic_test ,business.industry ,Cross-sectional study ,Biochemistry (medical) ,Clinical Biochemistry ,Area under the curve ,tau Proteins ,medicine.disease ,Plasma biomarkers ,Alzheimer Disease ,Internal medicine ,Diagnostic model ,medicine ,Biomarker (medicine) ,Humans ,Alzheimer's disease ,business ,Biomarkers - Abstract
BackgroundThe ultrasensitive detection of blood-based biomarkers such as amyloid β (Aβ), tau, and neurofilament light (NFL) has drawn much attention in Alzheimer disease (AD) diagnosis. However, few studies have been conducted in the Chinese population. This study aimed to evaluate the ability of plasma biomarker diagnostic models for AD in the Chinese population based on a novel digital immunoassay technology.Methods159 patients with AD, 148 patients with amnestic mild cognitive impairment (aMCI), and 121 cognitively normal control participants were recruited from 2 cohorts. The concentrations of plasma Aβ42, Aβ40, Aβ42/Aβ40, total tau (t-tau), phosphorylated tau 181 (p-tau 181), and NFL were quantified using an ultrasensitive single molecule array (Simoa) platform. Comprehensive and simplified diagnostic models were established based on the plasma biomarker profile and clinical characteristics.ResultsAmong all blood biomarkers, p-tau181 had the greatest potential for identifying patients with cognitive impairment. The simplified diagnostic model, which combined plasma p-tau181, Aβ42, and clinical features, achieved 93.3% area under the curve (AUC), 78.6% sensitivity, and 94.2% specificity for distinguishing AD from control participants, indicating a diagnostic ability approaching that of the comprehensive diagnostic model including 5 plasma biomarkers and clinical characteristics (95.1% AUC, 85.5% sensitivity, 94.2% specificity). Moreover, the simplified model reached 95.9% AUC and 94.0% AUC for early- and late-onset AD/control participants, respectively.ConclusionsWe established AD diagnostic models using plasma biomarkers for Chinese participants. These findings suggest the simplified diagnostic model provides an accessible and practical way for large-scale screening in the clinic and community, especially in developing countries.
- Published
- 2021
26. A facile polymer mediated dye incorporation method for fluorescence encoded microbeads with large encoding capacities
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Hajar Masoomi, Qingsheng Guo, Jiayu Zhang, Cang Chen, Hong Xu, Yunfei Ge, Hongchen Gu, and Yao Wang
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chemistry.chemical_classification ,Materials science ,Polymers ,Surface Properties ,Doping ,Static Electricity ,Metals and Alloys ,General Chemistry ,Polymer ,Fluorescence ,Catalysis ,Microspheres ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,chemistry ,Chemical engineering ,Microscopy, Fluorescence ,Materials Chemistry ,Ceramics and Composites ,Particle Size ,Mesoporous material ,Porosity ,Fluorescent Dyes - Abstract
Here we report a facile dye incorporation method for fluorescence encoded microbeads, which is achieved by tuning the mixed polymer type (blank and dye-labeled polymers) and their doping ratio through electrostatic loading into mesoporous beads. This method is universal to various carriers and could render large encoding capacities.
- Published
- 2021
27. Development of an Antibacterial Bone Graft by Immobilization of Levofloxacin Hydrochloride-Loaded Mesoporous Silica Microspheres on a Porous Scaffold Surface
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Yi Zuo, Dongmei Fan, Jiaxing Jiang, Hongchen Gu, Yan Yan, Yao Wang, Xinguang Yang, Jidong Li, Jiawei Wei, and Li Yubao
- Subjects
Scaffold ,Silicon dioxide ,0206 medical engineering ,Biomedical Engineering ,Pharmaceutical Science ,Medicine (miscellaneous) ,Bioengineering ,Levofloxacin ,02 engineering and technology ,Chitosan ,chemistry.chemical_compound ,General Materials Science ,Polyurethane ,Tissue Scaffolds ,Mesoporous silica ,Silicon Dioxide ,021001 nanoscience & nanotechnology ,020601 biomedical engineering ,Microspheres ,Anti-Bacterial Agents ,Durapatite ,chemistry ,Drug delivery ,Surface modification ,0210 nano-technology ,Antibacterial activity ,Porosity ,Nuclear chemistry - Abstract
An effective local drug delivery system remains an urgently needed product for the treatment of chronic osteomyelitis in the clinic. In this study, we developed an antibacterial functionalization bone graft by immobilizing levofloxacin hydrochloride-loaded mesoporous silica microspheres (LFH @ MSNs) on the surface of a nanohydroxyapatite/polyurethane (n-HA/PU) bioactive composite scaffold. Through pretreatment of the n-HA/PU scaffold by chitosan solution and subsequent crosslinking by vanillin, LFH @ MSNs were uniformly and stably immobilized on the scaffold surface. The results of drug release experiments showed that the release of LFH from LFH @ MSN-modified n-HA/PU scaffolds (LFH @ MSN/n HA/PU) lasted up to 42d. The antibacterial assays indicated that LFH @ MSN/n-HA/PU offers satisfactory antibacterial activity against both gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli) bacteria. The biosafety assays demonstrated that the LFH @ MSN/n-HA/PU scaffold could satisfy the requirements of the biosafety standards. The constructed LFH @ MSN/n-HA/PU porous scaffolds with an antibacterial surface and favorable biosafety are deemed a promising candidate for infectious bone defect repair.
- Published
- 2019
28. Quick synthesis of a novel combinatorial delivery system of siRNA and doxorubicin for a synergistic anticancer effect
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Fan Li, Yijie Chen, Fang Wang, Hongchen Gu, Mengchun Chen, Weiliang Xia, and Ledan Wang
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Drug ,media_common.quotation_subject ,Cell ,Biophysics ,Pharmaceutical Science ,Bioengineering ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Biomaterials ,Drug Discovery ,medicine ,Gene silencing ,Doxorubicin ,media_common ,Chemistry ,Organic Chemistry ,General Medicine ,Transfection ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Multiple drug resistance ,medicine.anatomical_structure ,Cancer research ,Delivery system ,Nanocarriers ,0210 nano-technology ,medicine.drug - Abstract
Purpose: Combining siRNA and other chemotherapeutic agents into one nanocarrier can overcome the multidrug resistance (MDR) phenomenon by synergistically MDR relative genes silencing and elevated chemotherapeutic activity. Most of these systems are typically fabricated through complicated procedures, which involves materials preparation, drug loading and modifications. Herein, the purpose of this study is to develop a new and fast co-delivery system of siRNA and doxorubicin for potentially synergistic cancer treatment. Methods: The co-delivery system is constructed conveniently by a stable complex consisting of doxorubicin bound to siRNA via intercalation firstly, followed by interacting with (3-Aminopropyl)triethoxysilane (APTES) electrostatically and Tetraethyl orthosilicate (TEOS) co-condensed, and the characterizations of the resultant nanocarrier are also investigated. Furthermore, this study evaluates the synergistic anti-cancer efficacy in MCF-7/MDR cells after treatment of siRNA and doxorubicin 'two in one' nanocarriers. Results: We establish a new and fast method to craft a co-delivery system of siRNA and doxorubicin with controllable and nearly uniform size, and the entire fabrication process only costs in about 10 minutes. The resultant co-delivery system presents high loading capacities of siRNA and doxorubicin, and the encapsulated doxorubicin plays a pH-responsive control release. Further, biological functionality tests of the synthesized co-delivery nanocarriers show high inhibition of P-gp protein encoded by MDR-1 gene in MCF-7/MDR cells (a variant of human breast cancer cell line with drug resistance) after transfection of these nanocarriers carrying MDR-1 siRNA and doxorubicin simultaneously, which sensitize the MCF-7/MDR cells to doxorubicin, overall leading to improved cell suppression. Conclusion: Collectively, this co-delivery system not only serves as potent therapeutics for synergistic cancer therapy, it also may facilitate the bench-to-bedside translation of combinatorial delivery system as a robust drug nanocarrier by allowing for fabricating a simply and fast nanocarrier for co-delivery of siRNA and doxorubicin with predictable high production rate.
- Published
- 2019
29. Determination of the Binding Constant between Oligonucleotide-Coupled Magnetic Microspheres and Target DNA
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Hongchen Gu, Xiaomin Chen, Mengting Zhou, Xiaoxia Fang, Hao Yang, and Hong Xu
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Thesaurus (information retrieval) ,Oligonucleotide ,Chemistry ,General Chemical Engineering ,General Chemistry ,Computational biology ,Binding constant ,Microsphere ,lcsh:Chemistry ,chemistry.chemical_compound ,Search engine ,lcsh:QD1-999 ,Gene ,DNA - Abstract
Oligonucleotide-coupled magnetic microspheres (PMPs) are commonly used as solid carriers in genetic analysis to specifically recognize, capture, and manipulate target DNA. Determining the binding c...
- Published
- 2019
30. A spherical poly(acrylic acid) brush–enzyme block with high catalytic capacity for signal amplification in digital biological assays
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Jingwei Yi, Jianlong Zhao, Hongchen Gu, Zehang Gao, Hong Xu, Hongbo Zhou, Yibei Wang, and Xiaoxia Fang
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chemistry.chemical_classification ,General Chemical Engineering ,Biomolecule ,Nanoparticle ,02 engineering and technology ,General Chemistry ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,Fluorescence ,Signal ,0104 chemical sciences ,Enzyme binding ,chemistry.chemical_compound ,chemistry ,Chemical engineering ,Fluorescence microscope ,Digital signal ,0210 nano-technology ,Acrylic acid - Abstract
Ultrasensitive determination of some ultra-low abundance biological molecules closely related to diseases is currently a wide concern and urgent issue to be addressed. Here, a spherical poly(acrylic acid)–alkaline phosphatase (SP–AKP) signal amplification block using spherical poly(acrylic acid) brush nanoparticles (SP) as the immobilized carriers was designed and synthesized optimally first. The results show that a single SP–AKP with high enzyme binding capacity and high catalytic ability (up to about 4800 effective free AKP per SP–AKP) has much greater fluorescence signal amplification ability than a single free AKP or SiO2–COOH–AKP. Then, a droplet generation microfluidic chip was prepared successfully, and the SP–AKP was loaded and confined in a 14 pL droplet by adjusting its concentration to ensure at most one SP–AKP was encapsulated in each droplet according to Poisson's theory. Finally, the fluorescence signals produced by 4-methylumbelliferyl phosphate (4-MUP) catalyzed via SP–AKP within 6 min were sufficient to be detected by a fluorescence microscope. Thus, the digital signal distribution of “1/0” (signal/background) was obtained, making this SP–AKP signal amplification block a promising enzyme label for potential high sensitivity digital biological detection applications.
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- 2019
31. A T1/T2 dual functional iron oxide MRI contrast agent with super stability and low hypersensitivity benefited by ultrahigh carboxyl group density
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Hongchen Gu, Fenglin Hu, Yuanpeng Rui, Chongchong Miao, and Yourong Duan
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Materials science ,Biocompatibility ,MRI contrast agent ,Dispersity ,Biomedical Engineering ,Iron oxide ,Nanoparticle ,02 engineering and technology ,General Chemistry ,General Medicine ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Iron sucrose ,01 natural sciences ,0104 chemical sciences ,Ferumoxytol ,chemistry.chemical_compound ,Colloid ,chemistry ,medicine ,General Materials Science ,0210 nano-technology ,Nuclear chemistry ,medicine.drug - Abstract
Clinically acceptable safety and efficacy are the most important issues for the design and synthesis of iron oxide MRI contrast agents. In order to meet the practical requirements, a kind of low molecular weight PAA-coated Fe3O4 nanoparticle (CS015) with super colloidal stability and low hypersensitivity benefitting from an ultrahigh carboxyl group density was developed in this study. The composition and physicochemical properties of the particles were characterized by TEM, XRD, FTIR and TGA. The ultrahigh density of COOH on the particles (33 COOH per nm2) was verified while a core size of 5.1 nm and a dynamic diameter of 41 nm with a narrow distribution were also achieved. The particles still showed excellent dispersity and stability even after a spray-drying or freeze-drying process, exposure to high temperature sterilized conditions and long-term storage. The nanoparticles could quickly capture iron ions in bulk solution which was confirmed by ITC results, and the bioactive iron concentration of CS015 was greatly decreased (0.54 ± 0.05 mg L-1) compared to that of commercially available ferumoxytol, iron sucrose and VSOP. Free iron ion release was 1120 times lower than the toxic concentration of iron. An excellent biocompatibility of CS015 with no obvious cytotoxicity and low risk of hypersensitivity has been manifested by cytotoxicity experiments and a passive cutaneous anaphylaxis test. The T1 and T2-weighted MRI contrast effects both in vitro and in vivo have also been verified which made CS015 a potential dual MRI contrast agent. Furthermore, theoretically calculated conformation was speculated and all the advantages mentioned above were benefited from the three dimensional brush-like texture of CS015. Therefore, these merits make the CS015 nanoplatform highly suitable in diagnostic applications as a MRI contrast agent.
- Published
- 2019
32. Tuning of surface protein adsorption by spherical mixed charged silica brushes (MCB) with zwitterionic carboxybetaine component
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Hongchen Gu, Fenglin Hu, Kaimin Chen, and Hong Xu
- Subjects
Immobilized enzyme ,Chemistry ,Biomedical Engineering ,Chain transfer ,02 engineering and technology ,General Chemistry ,General Medicine ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Methacrylate ,01 natural sciences ,0104 chemical sciences ,End-group ,Adsorption ,Polymerization ,Polymer chemistry ,Copolymer ,General Materials Science ,0210 nano-technology ,Protein adsorption - Abstract
Controlled protein adsorption and release without deformation and loss of activity under mild conditions is an essential issue for biological carriers. A spherical mixed charged silica brush (MCB), which could tune protein adsorption, has been prepared by introducing zwitterionic carboxybetaine copolymer onto the surface of silica nanoparticles for the first time. The simple surface-initiated reversible addition–fragmentation chain transfer polymerization (SI-RAFT) was applied to synthesize the MCB precursor – poly(2-(dimethylamino)ethyl methacrylate) modified silica nanoparticles (SiO2@PDMAEMA). Then, the end group in PDMAEMA was quaternized with propiolactone to obtain poly(DMAEMA-co-carboxybetaine methacrylate) modified silica nanoparticles (SiO2@poly(DMAEMA-co-CBMA)), which was denoted as MCB. In comparison, fully quaternized MCB (SiO2@PCBMA) was also prepared by a one-step strategy. Physicochemical behaviours of MCB in solution were systematically studied. The zwitterionic CBMA component endows the MCB with tunable adsorption towards both acidic and basic proteins through simple adjustment of the DMAEMA to CBMA ratio under mild conditions. This study may have great potential applications in the biomedical field, including tunable drug loading and releasing, and immobilized enzymes, etc.
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- 2020
33. Modulation of the structural properties of mesoporous silica nanoparticles to enhance the T
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Didem, Şen Karaman, Diti, Desai, Jixi, Zhang, Sina, Tadayon, Gözde, Unal, Jarmo, Teuho, Jawad, Sarfraz, Jan-Henrik, Smått, Hongchen, Gu, Tuomas, Näreoja, and Jessica M, Rosenholm
- Abstract
In this study, we have investigated the contrast enhancement of Gd(iii) incorporated nanoparticle-based contrast agents (CA) by the modulation of the synthesis and structural parameters of the mesoporous silica nanoparticle (MSN) matrix. In the optimisation process, the structure of the MSN matrix, post-synthesis treatment protocols, as well as the source and incorporation routes of paramagnetic gadolinium centers were considered, with the aim to shorten the T
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- 2020
34. A T
- Author
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Chongchong, Miao, Fenglin, Hu, Yuanpeng, Rui, Yourong, Duan, and Hongchen, Gu
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Drug Stability ,Cell Survival ,Cell Line, Tumor ,Iron ,Passive Cutaneous Anaphylaxis ,Acrylic Resins ,Hypersensitivity ,Contrast Media ,Humans ,Magnetite Nanoparticles ,Magnetic Resonance Imaging - Abstract
Clinically acceptable safety and efficacy are the most important issues for the design and synthesis of iron oxide MRI contrast agents. In order to meet the practical requirements, a kind of low molecular weight PAA-coated Fe
- Published
- 2020
35. Multiplexed Luminescence Oxygen Channeling Immunoassay Based on Dual-Functional Barcodes with a Host-Guest Structure: A Facile and Robust Suspension Array Platform
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Hongchen Gu, Hong Xu, Jianping Fu, Yao Wang, Cang Chen, Dan Wei, and Qingsheng Guo
- Subjects
Analyte ,Luminescence ,Computer science ,02 engineering and technology ,010402 general chemistry ,Barcode ,01 natural sciences ,Multiplexing ,law.invention ,Biomaterials ,Suspension array technology ,law ,Quantum Dots ,medicine ,General Materials Science ,Multiplex ,Immunoassay ,medicine.diagnostic_test ,Singlet Oxygen ,business.industry ,General Chemistry ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Oxygen ,Optoelectronics ,0210 nano-technology ,business ,Decoding methods ,Biotechnology - Abstract
The development of a powerful immunoassay platform with capacities of both simplicity and high multiplexing is promising for disease diagnosis. To meet this urgent need, for the first time, a multiplexed luminescent oxygen channeling immunoassay (multi-LOCI) platform by implementation of LOCI with suspension array technology is reported. As the microcarrier of the platform, a unique dual-functional barcode with a host-guest structure composed of a quantum dot host bead (QDH) and LOCI acceptor beads (ABs) is designed, in which QDH provides function of high coding capacity while ABs facilitate the LOCI function. The analytes bridge QDH@ABs and LOCI donor beads (DBs) into a close proximity, forming a QDH@ABs-DBs "host-guest-satellite" superstructure that generates both barcode signal from QDH and LOCI signal induced by singlet oxygen channeling between ABs and DBs. Through imaging-based decoding, different barcodes are automatically distinguished and colocalized with LOCI signals. Importantly, the assay achieves simultaneous detection of multiple analytes within one reaction, simply by following a "mix-and-measure" protocol without the need for tedious washing steps. Furthermore, the multi-LOCI platform is validated for real sample measurements. With the advantages of robustness, simplicity, and high multiplexing, the platform holds great potential for the development of point-of-care diagnostics.
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- 2019
36. Evaluation of a simple versus composite plasma biomarker model as screening strategy for the diagnosis of cognitive impairment in Chinese population
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Jingwei Yi, Saineng Ding, Qianhua Zhao, Hong Xu, Ding Ding, Wanqing Wu, Li Zheng, Xue Wu, Xiaoniu Liang, Zhenxu Xiao, and Hongchen Gu
- Subjects
Oncology ,medicine.medical_specialty ,Chinese population ,Neurology ,business.industry ,Internal medicine ,medicine ,Biomarker (medicine) ,Neurology (clinical) ,Cognitive impairment ,business - Published
- 2021
37. Three-Dimensional Barcodes with Ultrahigh Encoding Capacities: A Flexible, Accurate, and Reproducible Encoding Strategy for Suspension Arrays
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Dan Wei, Hongchen Gu, Hong Xu, Hao He, Xunbin Wei, Lu Si, Shunjia Zhang, Ding Sheng-zi Zhang, and Ye Lin
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Computer science ,General Chemical Engineering ,Nanotechnology ,02 engineering and technology ,General Chemistry ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Barcode ,01 natural sciences ,Fluorescence ,0104 chemical sciences ,law.invention ,Quantum dot ,Proof of concept ,law ,Encoding (memory) ,Materials Chemistry ,Multiplex ,0210 nano-technology - Abstract
Novel 3D barcodes with an extraordinarily high encoding capacity are developed through a flexible, accurate, and reproducible method. Here, the three dimensions refer to the size, fluorescence emission wavelength, and intensity of the barcodes. As a proof of concept, a 3D barcode library with an encoding capacity of 100 flow cytometry-distinguishable barcodes is achieved successfully by combining the multiscaled host particles with a set of guest nanoparticles owning to their individual different fluorescent intensity via an ingenious host–guest structure, where fluorescein isothiocyanate and a kind of quantum dots are separately loaded inside. Five-plexed tumor marker detection is further implemented, and the results demonstrate the strong feasibility of 3D barcodes in multiplex assays.
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- 2017
38. A tailored LNA clamping design principle: Efficient, economized, specific and ultrasensitive for the detection of point mutations
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Hongchen Gu, Xu Gaolian, Lin Zhang, Yuchen Han, Xiaohua Qian, Ruiying Zhao, Hao Yang, Hong Xu, and Mengqiu Yan
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Peptide Nucleic Acids ,biology ,business.industry ,Computer science ,Point mutation ,Oligonucleotides ,General Medicine ,Computational biology ,Gene mutation ,Constriction ,Polymerase Chain Reaction ,Applied Microbiology and Biotechnology ,law.invention ,law ,Mutation ,Gene duplication ,Mutation (genetic algorithm) ,biology.protein ,Point Mutation ,Molecular Medicine ,Suppressor ,Personalized medicine ,Epidermal growth factor receptor ,Locked nucleic acid ,business - Abstract
In the development of personalized medicine, the ultrasensitive detection of point mutations that correlate with diseases is important to improve the efficacy of treatment and guide clinical medication. In this study, locked nucleic acid (LNA) was introduced as an amplification suppressor of a massive number of wild-type alleles in an amplification refractory mutation system (ARMS) to achieve the detection of low-abundance mutations with high specificity and sensitivity of at least 0.1%. By integrating the length of clamp, base type, number and position of LNA modifications, we have established a "shortest length with the fewest LNA bases" principle from which each LNA base would play a key role in the affinity and the ability of single base discrimination could be improve. Finally, based on this LNA design guideline, a series of the most important single point mutation sites of epidermal growth factor receptor (EGFR) was verified to achieve the optimal amplification state which as low as 0.1% mutation gene amplification was not affected under the wild gene amplification was completely inhibited, demonstrating that the proposed design principle has good applicability and versatility and is of great significance for the detection of circulating tumor DNA. This article is protected by copyright. All rights reserved.
- Published
- 2021
39. Development of a Plasma Biomarker Diagnostic Model Incorporating Ultrasensitive Digital Immunoassay as a Screening Strategy for Alzheimer Disease in a Chinese Population.
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Xue Wu, Zhenxu Xiao, Jingwei Yi, Saineng Ding, Hongchen Gu, Wanqing Wu, Jianfeng Luo, Xiaoniu Liang, Li Zheng, Hong Xu, Qianhua Zhao, and Ding Ding
- Published
- 2021
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40. Multiplexed Detection: Precisely Encoded Barcodes through the Structure‐Fluorescence Combinational Strategy: A Flexible, Robust, and Versatile Multiplexed Biodetection Platform with Ultrahigh Encoding Capacities (Small 19/2021)
- Author
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Cang Chen, Hajar Masoomi, Jiancong Wu, Hongchen Gu, Yimei Cao, Jian Ye, Jing He, Qingsheng Guo, Jingwei Yi, Chongzhao Wu, Xiaomei Chi, Hong Xu, Yao Wang, and Xiaoxia Fang
- Subjects
Biomaterials ,business.industry ,Computer science ,Encoding (memory) ,General Materials Science ,General Chemistry ,business ,Fluorescence ,Multiplexing ,Computer hardware ,Biotechnology - Published
- 2021
41. Precisely Encoded Barcodes through the Structure‐Fluorescence Combinational Strategy: A Flexible, Robust, and Versatile Multiplexed Biodetection Platform with Ultrahigh Encoding Capacities
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Jingwei Yi, Qingsheng Guo, Xiaoxia Fang, Yimei Cao, Jiancong Wu, Yao Wang, Jing He, Xiaomei Chi, Chongzhao Wu, Hong Xu, Hongchen Gu, Cang Chen, Hajar Masoomi, and Jian Ye
- Subjects
Materials science ,Nanotechnology ,02 engineering and technology ,010402 general chemistry ,Barcode ,01 natural sciences ,Multiplexing ,law.invention ,Biomaterials ,Suspension array technology ,law ,Encoding (memory) ,Quantum Dots ,General Materials Science ,Electronic Data Processing ,General Chemistry ,Flow Cytometry ,021001 nanoscience & nanotechnology ,Single excitation ,Fluorescence ,Microspheres ,0104 chemical sciences ,Quantum dot ,Nanoparticles ,Magnetic nanoparticles ,0210 nano-technology ,Biotechnology - Abstract
With the rapid development of suspension array technology, microbeads-based barcodes as the core element with sufficient encoding capacity are urgently required for high-throughput multiplexed detection. Here, a novel structure-fluorescence combinational encoding strategy is proposed for the first time to establish a barcode library with ultrahigh encoding capacities. Based on the never revealed transformability of the structural parameters (e.g., porosity and matrix component) of mesoporous microbeads into scattering signals in flow cytometry, the enlargement of codes number has been successfully realized in combination with two other fluorescent elements of fluorescein isothiocyanate isomer I (FITC) and quantum dots (QDs). The barcodes are constructed with precise architectures including FITC encapsulated within mesopores and magnetic nanoparticles as well as QDs immobilized on the outer surface to achieve the ultrahigh encoding level of 300 accompanied with superparamagnetism. To the best of knowledge, it is the highest record of single excitation laser-based encoding capacity up to now. Moreover, a ten-plexed tumor markers bioassay based on the tailored-designed barcodes has been evaluated to confirm their feasibility and effectiveness, and the results indicate that the barcodes platform is a promising and robust tool for practical multiplexed biodetection.
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- 2021
42. Construction of macroinitiators labeled magnetic spheres as a notable signal amplification system for biosensing
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Hongchen Gu, Hong Xu, Jiancong Wu, and Yao Wang
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chemistry.chemical_classification ,Materials science ,Atom-transfer radical-polymerization ,Mechanical Engineering ,02 engineering and technology ,Polymer ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,01 natural sciences ,Combinatorial chemistry ,Fluorescence ,digestive system diseases ,0104 chemical sciences ,Electron transfer ,Polymerization ,chemistry ,Mechanics of Materials ,General Materials Science ,SPHERES ,0210 nano-technology ,Signal amplification ,Biosensor - Abstract
Here we report macroinitiators labeled magnetic spheres (MSs) as a notable signal amplification system for biosensing. The macroinitiators as labels with multiple initiators on each polymer backbone facilitate the polymerization process for fluorescent signal amplification, while the carriers of micro-sized MSs are beneficial to reaction kinetics and could be rapidly read via flow cytometer in a high-throughput way. By utilizing an optimal two-step activators generated electron transfer for atom transfer radical polymerization (AGET ATRP) reaction, our proposed macroinitiators labeled MSs strategy exhibits a significantly superior fluorescent signal amplification effect when compared to conventional dye-labeled MSs, indicating the promising potential for biosensing in diagnostic fields.
- Published
- 2021
43. Extraction, detection, and profiling of serum biomarkers using designed Fe3O4@SiO2@HA core–shell particles
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Jiatao Lou, Hongchen Gu, Kun Qian, Bin Liu, Jingjing Wan, Ru Zhang, Xuming Sun, Wei Xu, Xuechao Pang, Chandrababu Rejeeth, and Wei Yan
- Subjects
Detection limit ,Chromatography ,Chemistry ,Sample complexity ,02 engineering and technology ,Standard solution ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,Serum samples ,Mass spectrometry ,01 natural sciences ,Atomic and Molecular Physics, and Optics ,0104 chemical sciences ,Core shell ,Serum biomarkers ,Proteome ,General Materials Science ,Electrical and Electronic Engineering ,0210 nano-technology - Abstract
Serum biomarkers in the form of proteins (e.g. cluster of differentiation-44 (CD44)) have been demonstrated to have high clinical sensitivity and specificity for disease diagnosis and prognosis. Owing to the high sample complexity and low molecular abundance in serum, the detection and profiling of biomarkers rely on efficient extraction by materials and devices, mostly using immunoassays via antibody-antigen recognition. Antibody-free approaches are promising and need to be developed for real-case applications in serum to address the limitations of antibody-based techniques in terms of robustness, expense, and throughput. In this work, we demonstrated a novel approach using hyaluronic acid (HA)-modified materials/devices for the extraction, detection, and profiling of serum biomarkers via ligand-protein interactions. We constructed Fe3O4@SiO2@HA particles with different sizes through layer-by-layer assembly and for the first time applied HA-functionalized particles in the facile extraction and sequence identification of CD44 in serum by mass spectrometry. We also first validated HA-CD44 binding through electrochemical sensing using HA-modified electrodes in both standard solutions and diluted serum samples, achieving a detection limit of ∼0.6 ng/mL and a linear response range from 1 ng/mL to 10 μg/mL. Furthermore, we performed profiling of HA-binding serum proteome, providing a new preliminary benchmark for the construction of future databases, and we investigated selected surface chemistries of particles for the capture of proteins in serum. Our work not only resulted in the development of a platform technology for CD44 extraction/detection and HA-binding proteome identification, but also guided the design of ligand affinity-based approaches for antibody-free analysis of serum biomarkers towards diagnostic applications.
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- 2017
44. Size-dependent optical properties of conjugated polymer nanoparticles
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Chaoqing Dong, Hong Xu, Fengwen Cao, Liqin Xiong, Hongchen Gu, and Ye Lin
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chemistry.chemical_classification ,Brightness ,Materials science ,General Chemical Engineering ,Fluorescence spectrometry ,Nanoparticle ,Fluorescence correlation spectroscopy ,Nanotechnology ,02 engineering and technology ,General Chemistry ,Polymer ,Conjugated system ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,Fluorescence ,0104 chemical sciences ,chemistry ,Nano ,0210 nano-technology - Abstract
A strong and stable fluorescent signal is the crux for the ultrasensitive biodetection technology, conjugated polymer nanoparticles (CPNs) as new fluorescence labels have attracted more and more attention for their excellent optical properties. However, a systematic understanding of the size-dependent optical properties of CPNs with diameters from the nano to submicron ranges is lacking, which is the most important issue when choosing label materials. Hence, poly[(9,9-dioctylfluorenyl-2,7-diyl)-co-(1,4-benzo-{2,1′,3}-thiadiazole)] (PFBT) nanoparticles with sizes from 50 nm to 200 nm were synthesized and studied. It was demonstrated that the spectroscopic and fluorescent properties are similar for CPNs with different sizes. The relationship between single-particle brightness and diameter was investigated via fluorescence spectrometry and fluorescence correlation spectroscopy (FCS), and the results presented that the single-particle brightness increased quadratically with the increase of the diameter of CPNs. This research may provide valuable support to further application of CPNs in biological diagnostics.
- Published
- 2017
45. In vitro and in vivo combined antibacterial effect of levofloxacin/silver co-loaded electrospun fibrous membranes
- Author
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Xinyu Huang, Wei Wu, Hongchen Gu, Wenguo Cui, Yongjie Ma, Guanggai Xia, Wasim Kapadia, Yao Wang, Zhiyong Sun, and Ziliang Song
- Subjects
medicine.medical_specialty ,Materials science ,Biomedical Engineering ,02 engineering and technology ,General Chemistry ,General Medicine ,Mesoporous silica ,Bacterial growth ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Antimicrobial ,01 natural sciences ,In vitro ,Electrospinning ,0104 chemical sciences ,Surgery ,Membrane ,Levofloxacin ,In vivo ,medicine ,General Materials Science ,0210 nano-technology ,medicine.drug ,Nuclear chemistry - Abstract
Post-surgery mesh infections are one of the most common complications of hernia repair at the interface of implant materials and tissue, because high doses of antimicrobial agents are toxic and low doses of antibacterial agents are ineffective, with no good clinical solution currently available. To reduce the infection rates after mesh implantation, we designed a "one-pot synthesized" mesoporous silica nanoplatform consisting of levofloxacin (Lev) and silver (Lev@MSN@Ag) composites with poly-l-lactide (PLLA) electrospun fibrous membranes via blending electrospinning. With advances in the combined antibacterial agents Lev and Ag at a low dosage for the treatment of drug-resistant bacterial infections (28 μg mL-1 Lev and 12 μg mL-1 Ag) with a concentration of 5 × 105 CFU mL-1, the composite electrospun fibers act as a carrier for drug-loading and have an antibacterial effect over 8 weeks. Lev@MSN@Ag-PLLA fibers showed a superior antibacterial effect on drug resistant strains in the in vitro test at low doses of antibacterial agents. Further, the in vivo study showed that Lev@MSN@Ag-PLLA fibers significantly inhibited bacterial growth and infection over 8 weeks through the combined effect of low dosage antibacterial drugs. In conclusion, the Lev@MSN@Ag-PLLA fibers provided an advanced combined antibacterial nanoplatform of low dosage for the treatment of drug-resistant bacterial infections.
- Published
- 2017
46. Use of Ultrasmall Superparamagnetic Iron Oxide Enhanced Susceptibility Weighted Imaging and Mean Vessel Density Imaging to Monitor Antiangiogenic Effects of Sorafenib on Experimental Hepatocellular Carcinoma
- Author
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Fang Lu, Zhi-hong Han, Hongchen Gu, Shuohui Yang, Jiang Lin, and Caixia Fu
- Subjects
Niacinamide ,Sorafenib ,lcsh:Medical technology ,Carcinoma, Hepatocellular ,Article Subject ,Angiogenesis Inhibitors ,Ferric Compounds ,030218 nuclear medicine & medical imaging ,Neovascularization ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Vessel density ,medicine ,Carcinoma ,Animals ,Humans ,Radiology, Nuclear Medicine and imaging ,Neovascularization, Pathologic ,medicine.diagnostic_test ,business.industry ,Ultrasmall superparamagnetic iron oxide ,Phenylurea Compounds ,Liver Neoplasms ,Magnetic resonance imaging ,medicine.disease ,Magnetic Resonance Imaging ,digestive system diseases ,lcsh:R855-855.5 ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Susceptibility weighted imaging ,Heterografts ,medicine.symptom ,business ,Nuclear medicine ,Research Article ,medicine.drug - Abstract
We investigated effectiveness of ultrasmall superparamagnetic iron oxide enhanced susceptibility weighted imaging (USPIO-enhanced SWI) and mean vessel density imaging (Q) in monitoring antiangiogenic effects of Sorafenib on orthotopic hepatocellular carcinoma (HCC). Thirty-five HCC xenografts were established. USPIO-enhanced SWI and Q were performed on a 1.5 T MR scanner at baseline, 7, 14, and 21 days after Sorafenib treatment. Intratumoral susceptibility signal intensity (ITSS) and Q were serially measured and compared between the treated (n = 15) and control groups (n = 15). Both ITSS and Q were significantly lower in the treated group at each time point (P < 0.05). Measurements in the treated group showed that ITSS persisted at 7 days (P = 0.669) and increased at 14 and 21 days (P < 0.05), while Q significantly declined at 7 days (P = 0.028) and gradually increased at 14 and 21 days. In the treated group, significant correlation was found between Q and histologic microvessel density (MVD) (r = 0.753, P < 0.001), and ITSS correlated well with MVD (r = 0.742, P = 0.002) after excluding the data from baseline. This study demonstrated that USPIO-enhanced SWI and Q could provide novel biomarkers for evaluating antiangiogenic effects of Sorafenib on HCC.
- Published
- 2017
47. Ultrabright dye-loaded spherical polyelectrolyte brushes and their fundamental structure-fluorescence tuning principles
- Author
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Peirui Wang, Hong Xu, Xiaoxia Fang, Yao Wang, Hajar Masoomi, Hongchen Gu, Cang Chen, and Kai Liu
- Subjects
chemistry.chemical_classification ,Materials science ,Doping ,Quantum yield ,Nanotechnology ,Polymer ,Fluorescence ,chemistry.chemical_compound ,chemistry ,Quantum dot ,Particle ,General Materials Science ,Chemical binding ,Acrylic acid - Abstract
Ultrabright fluorescent particles (UFPs) have attracted increasing attention because of their outstanding signal amplification functions. However, there is still an urgent demand for designing novel UFPs with new components or structures as the existing ones can not satisfy the practical requirements due to their inherent disadvantages. Here we propose a novel ultrabright fluorescent particle platform by doping dyes of 5-aminofluorescein (5-AF) into silica core-based spherical poly (acrylic acid) brushes (SiO2@PAA@5-AF) and discuss their fundamental structure-fluorescence tuning principles. A series of brushes with different polymer chain lengths are successfully synthesized and then loaded with 5-AF through chemical binding. The high loading amount, suitable density or distribution, and enhanced quantum yield (QY) of 5-AF due to the amide bond formation with PAA chains on brushes are concluded as the three major reasons for the ultrabrightness of SiO2@PAA@5-AF. Therefore, a 2350 ± 445 times brighter brush particle in comparison to a single quantum dot (QD) is realized, and a 2.1 ± 0.4 times fluorescence improvement of a brush vs. a QD normalized by volume is also achieved when taking the hydrodynamic diameter into consideration (∼300 nm vs. ∼30 nm). Moreover, the excellent tolerance stabilities in normally applied environments and outstanding label effects to form 4-plexed encoded beads are demonstrated as well. The results in this work strongly indicate a promising potential of SiO2@PAA@5-AF as an ultrabright and stable signal amplification tool for biomedical related sensing, labeling, and biodetection.
- Published
- 2019
48. Multiplexed Detection of Mutant Circulating Tumor DNA Using Peptide Nucleic Acid Clamping Asymmetric Polymerase Chain Reaction and Liquidchip
- Author
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Jiatao Lou, Hongchen Gu, Hong Xu, Xiaomin Chen, Qiaomei Guo, Ding Sheng-zi Zhang, and Lin Wang
- Subjects
Peptide Nucleic Acids ,Lung Neoplasms ,0206 medical engineering ,Mutant ,Biomedical Engineering ,Peptide Nucleic Acid Clamping ,Pharmaceutical Science ,Medicine (miscellaneous) ,Bioengineering ,Context (language use) ,02 engineering and technology ,medicine.disease_cause ,Polymerase Chain Reaction ,law.invention ,Circulating Tumor DNA ,chemistry.chemical_compound ,law ,Carcinoma, Non-Small-Cell Lung ,medicine ,Humans ,General Materials Science ,Digital polymerase chain reaction ,Protein Kinase Inhibitors ,Polymerase chain reaction ,Mutation ,Chemistry ,021001 nanoscience & nanotechnology ,020601 biomedical engineering ,Molecular biology ,Constriction ,ErbB Receptors ,genomic DNA ,0210 nano-technology ,DNA - Abstract
Circulating tumor DNA (ctDNA) in blood has been investigated as a feasible substitute for genetic alterations in tumor tissues to predict and assess drug responses, but current techniques of screening clinical relevant mutations still have great limitations in sensitivity, specificity, or multiplexed detection because of highly fragmented ctDNA and its low concentration in a high background of normal DNA. In this study, we developed PNA-aPCR-Liquidchip (PAPL), a novel method that aims to detect multiple mutant ctDNA. In order to demonstrate its utility, we analyzed three high frequent epidermal growth factor receptor (EGFR) mutations (exon 19 deletion, L858R, and T790M) in non-small cell lung cancer (NSCLC). Multiplexed analyses indicated that this method has high specificity and sensitivity which could detect down to 2∼5 copies of mutant EGFR in a background of 10,000 copies of wild-type genomic DNA, achieving the mutant abundance of 0.02%∼0.05%. Furthermore, PAPL had no significant differences with droplet digital PCR (ddPCR) in plasma cell-free DNA (cfDNA) detection. Thus, PAPL can be used to detect EGFR mutations in NSCLC patients' plasma, indicating that this method has great potential for application in the context of precision medicine based on mutant ctDNA detection.
- Published
- 2019
49. Droplets isolated array: A universal platform of delaying molecule cross-contamination between microdroplets for digital enzyme-based immunoassay
- Author
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Jianlong Zhao, Jingwei Yi, Hongchen Gu, Hongbo Zhou, Hong Xu, and Zehang Gao
- Subjects
endocrine system ,Materials science ,Fluorophore ,Diffusion ,Microfluidics ,02 engineering and technology ,010402 general chemistry ,complex mixtures ,01 natural sciences ,Signal ,chemistry.chemical_compound ,Materials Chemistry ,medicine ,Molecule ,Electrical and Electronic Engineering ,Instrumentation ,Detection limit ,medicine.diagnostic_test ,business.industry ,technology, industry, and agriculture ,Metals and Alloys ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,Fluorescence ,eye diseases ,0104 chemical sciences ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,chemistry ,Immunoassay ,Optoelectronics ,0210 nano-technology ,business - Abstract
Digital biodetection in picoliter-volume microdroplets has great potential for ultra-sensitivity detection due to the wide development of microfluidic technology and the high throughput of droplets generation. However, the diffusion of enzyme catalytic fluorescent products between droplets makes signal reading confused and inaccurate. Here, a spherical Poly (acrylic acid) Brushes immobilized Alkaline phosphatase (SP-AKP) as signal amplification block was synthesized and introduced into 14 pL droplet, and the SP-AKP digital detection was realized within only 6 min, which significantly improved the catalytic efficiency and shortened the detection time. Furthermore, aimed to decrease the diffusion rate of fluorophore between droplets, we proposed a Droplets Isolated Array (DIA) where droplets were trapped in chambers to keep them isolated. The DIA could trap ∼34,000 droplets once and reach 82.6 % of droplet coverage with high throughput and efficiency. Compared to conventional non-isolated droplets array, the DIA delayed the diffusion of fluorophore, and the reading time of droplet signal could be extended from 1 min to 30 min, which greatly improved the operability of the detection system and ensured the accuracy of the results. Finally, an accurate signal identification makes the limit of detection of SP-AKP achieve 309 aM.
- Published
- 2020
50. A stable USPIO capable for MR lymphography with ultra-low effective dosage
- Author
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Qinshan Li, Ying Nie, Hongchen Gu, Fenglin Hu, Yuanpeng Rui, and Chongchong Miao
- Subjects
Biomedical Engineering ,Cancer therapy ,Contrast Media ,Pharmaceutical Science ,Medicine (miscellaneous) ,Bioengineering ,02 engineering and technology ,03 medical and health sciences ,Mr lymphography ,medicine ,Animals ,Humans ,General Materials Science ,Magnetite Nanoparticles ,Lymph node ,030304 developmental biology ,0303 health sciences ,business.industry ,Lymphography ,Dextrans ,Image Enhancement ,021001 nanoscience & nanotechnology ,Magnetic Resonance Imaging ,Ferumoxytol ,medicine.anatomical_structure ,Lymphatic Metastasis ,Clinical diagnosis ,Molecular Medicine ,Lymph Nodes ,Rabbits ,Lymph ,Mr images ,0210 nano-technology ,Nuclear medicine ,business ,Superparamagnetic iron oxide - Abstract
Ultra-small superparamagnetic iron oxide (USPIO) nanoparticles appear to be promising tools for MR lymphography due to their unique magnetic properties. In clinical diagnosis, the effectiveness of USPIO will greatly affect the clinician's judgment to the enhanced MR images. In this study, we evaluated the effectiveness of CS015, a PAA-coated USPIO, with subcutaneous and intravenous administration. It appeared that subcutaneously injected particles had much higher efficiency to reach lymph nodes, and even worked at a very small dose 0.075 μmol/kg. Further, we compared CS015 with ferumoxytol and ferumoxtran-10 in MR lymphography and found that CS015 had the best performance. And the lymph node metastases in New Zealand rabbits were successfully detected using CS015 with one single dose. These merits of CS015 make it a promising MR lymphography contrast agent with potential applications in cancer therapy.
- Published
- 2020
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