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Purpose Nanoparticle (NP)-based chemo-photothermal therapy (CPT) has been shown to be a promising non-invasive approach for antitumor treatment. However, NPs must overcome the limitations of opsonization, clearance of the reticuloendothelial system, and ineffective targeting of tumor tissue sites. To solve these problems, stem cell membrane (SCM)-camouflaged polydopamine nanoparticles (PDA@SCM NPs) carrying the hydrophobic anticancer drug 7-ethyl-10-hydroxycamptothecin (SN38) were constructed for CPT of malignant bone tumors. Methods We developed umbilical-cord mesenchymal stem cell membrane-coated polydopamine nanoparticles encapsulating SN38 (PDA-SN38@SCM NPs) as an efficient tumor-targeting drug-delivery platform for CPT of malignant bone tumors. We characterized PDA@SCM NPs and evaluated the biocompatibility and anti-phagocytosis properties of PDA@SCM NPs. The antitumor activity of PDA-SN38@SCM NPs was evaluated in MG63 lines and an MG63 xenograft model in mice. Results Synthesized PDA-SN38@SCM NPs retained an excellent photothermal effect after SN38 loading. The drug release of PDA-SN38@SCM NPs could be triggered by near-infrared irradiation and an acidic stimulus. PDA@SCM NPs exhibited lower nonspecific macrophage uptake, longer retention in blood, and more effective accumulation at tumor sites than that shown by PDA NPs. Confocal laser scanning microscopy (CLSM) and flow cytometry showed that MG63 cells took up more PDA-SN38@SCM NPs than PDA-SN38 NPs. In vitro and in vivo antitumor studies demonstrated the outstanding performance of PDA-SN38@SCM NPs in synergistic CPT for bone tumors. Conclusion PDA-SN38@SCM NPs demonstrated an extraordinary synergistic CPT effect and could be a promising strategy for the treatment of malignant bone tumors.

Introduction Mesenchymal stem cells (MSCs) are a promising resource for tissue regeneration and repair. However, their clinical application is hindered by technical limitations related to MSC enrichment at the target sites. Methods MSCs were labeled with magnetic Fe3O4 nanoparticles (NPs). We analyzed the effects of NP on cell proliferation, stem cell characteristics, and cytokine secretion. Furthermore, we induced NP-labeled MSC migration with an external magnetic field toward laser-induced skin wounds in rats and evaluated the associated anti-inflammatory effects. Results Fe3O4 NP application did not adversely affect MSC characteristics. Moreover, Fe3O4 NP-labeled MSCs presented increased anti-inflammatory cytokine and chemokine production compared with unlabeled MSCs. Furthermore, MSCs accumulated at the injury site and magnetic targeting promoted NP-labeled MSC migration toward burn injury sites in vivo. On day 7 following MSC injection, reduced inflammation and promoted angiogenesis were observed in the magnetically targeted MSC group. In addition, anti-inflammatory factors were upregulated, whereas pro-inflammatory factors were downregulated within the magnetically targeted MSC group compared with those in the PBS group. Conclusion This study demonstrates that magnetically targeted MSCs contribute to cell migration to the site of skin injury, improve anti-inflammatory effects and enhance angiogenesis compared with MSC injection alone. Therefore, magnetically targeted MSC therapy may be an effective treatment approach for epithelial tissue injuries.

Purpose The primary goal of the present study was to design doxorubicin (DOX)-loaded superparamagnetic iron oxide (SPIO) nanoparticles (NPs) coated with mesenchymal stem cell (MSC) membranes and explore their effect on colon cancer in vitro and in vivo. Methods DOX-SPIO NPs were coated with MSC membranes using an extruder, and the morphological characteristics of MSC membrane-camouflaged nanodrug (DOX-SPIO@MSCs) evaluated by transmission electron microscopy (TEM) and NP-tracking analysis. Drug loading and pH response were assessed by UV spectrophotometry. Intracellular colocalization was analyzed using NP-treated MC38 cells stained with 3,3'-dioctadecyloxacarbocyanine perchlorate and Hoechst 33342. Cellular uptake was analyzed using an inverted fluorescence microscope and flow cytometry and cytotoxicity evaluated by cell counting kit-8 assay. Biological compatibility was assessed by hemolysis analysis, immunoactivation test and leukocyte uptake experiments. Furthermore, intravenous injection of chemotherapy drugs into MC38 tumor-bearing C57BL/6 mice was used to study anti-tumor effects. Results Typical core-shell NP structures were observed by TEM. Particle size remained stable in fetal bovine serum and phosphate-buffered saline (PBS). Compared with DOX-SPIO, DOX-SPIO@MSCs improved cellular uptake efficiency, enhanced anti-tumor effects, and reduced the immune system response. Animal experiments demonstrated that DOX-SPIO@MSCs enhanced tumor treatment efficacy while reducing systemic side effects. Conclusion Our experimental results demonstrate that DOX-SPIO@MSCs are a promising targeted nanocarrier for application in treatment of colon cancer.

Diabetes mellitus (DM) is characterized by the irreversible destruction of insulin-secreting pancreatic β-islet cells and requires life-long exogenous insulin therapy. Umbilical cord Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) have been shown to improve islet function in animal models of diabetes. However, inadequate MSC homing to injured sites has limited their efficacy. Since efficient cell therapy heavily relies on appropriate homing to target tissues, increasing the specificity to the target organ and the extent of homing of the injected WJ-MSCs is paramount to successful clinical outcomes. Therefore, in this study, we synthesized Fe3O4@polydopamine nanoparticle (NP)-labeled MSCs and evaluated their therapeutic efficacy in a clinically relevant rat model of streptozotocin-induced diabetes using an external magnetic field. We found that NPs were successfully incorporated into WJ-MSCs and did not negatively affect stem cell properties. Magnetic targeting of WJ-MSCs contributed to long-term cell retention in pancreatic tissue and improved the islet function of diabetic rats, compared to injection of WJ-MSC alone. In addition, anti-inflammatory effects and the anti-apoptotic capacity of WJ-MSCs appeared to play a major role in the functional and structural recovery of the pancreas. Thus, therapy relying on the magnetic targeting of WJ-MSCs may serve as an effective approach for DM treatment.

DEHP is reported to cause precocious puberty of females in both humans and rodents, but the underlying mechanisms were largely unknown. This study was designed to clarify the effects and the mechanisms of DEHP on the pathogenesis of sexual precocity. Prepubertal female rats were treated with DEHP for 4 weeks. Key organs were analyzed in control conditions and after exposure to 0.2, 1, and 5 mg/kg/day DEHP in pubertal female rats. To determine the role of the IGF-1/PI3K/Akt/mTOR signaling pathway in DEHP-induced female precocious puberty, 36 rats were treated with 5 mg/kg/day DEHP to establish a model of female precocious puberty. And we investigated the expression of genes and proteins related to IGF-1 pathway in rat hypothalamus after treatment with inhibitors. In the present study, we observed that DEHP treatment resulted in earlier vaginal opening time, higher number of Nissl bodies in the hypothalamus neurons, lower apoptosis of hypothalamic cells, higher IGF-1 and GnRH levels in the serum and hypothalamus. DEHP could also upregulated the expression of IGF-1/PI3K/Akt/mTOR pathway and GnRH in the hypothalamus of adolescent female rats, and inhibition of IGF-1R and mTOR in hypothalamus could block the activation of Kiss-1, GPR54, and GnRH by DEHP. In summary, our study suggested that DEHP might activate the hypothalamic GnRH neurons prematurely through the IGF-1 signaling pathway and promote GnRH release, leading to the initiation of female sexual development. Our results provide a new molecular mechanism underlying reproductive and developmental toxicity in pubertal female rats induced by DEHP.

Mesenchymal stem cell (MSC)-based therapy has emerged as a promising therapeutic strategy for tissue regeneration and repair. However, efficient targeted delivery to specific tissues remains an open challenge. Here, we non-invasively monitored the migration of MSCs labeled with Fe3O4@polydopamine nanoparticles (Fe3O4@PDA NPs) toward laser burn injury sites in a living rat model and evaluated the effects of the labeled MSCs at the injury site. The Fe3O4@PDA NPs could be effectively incorporated into the MSCs without any negative effects on stem cell properties. Furthermore, they enhanced the migration ability of the MSCs by up-regulating the expression level of C–X–C chemokine receptor type 4 (CXCR4). They also increased the secretion of some cytokines and the expression of healing-related genes in comparison with unlabeled MSCs. Labeled MSCs were intravenously administered into injured rats, and live imaging was performed to monitor MSC migration. Fluorescent signals of the labeled MSCs appeared at burn injury lesions 1 day after injection and then gradually increased up to 7 days. After 7 days, the group injected with the labeled MSCs showed less inflammation compared with those injected with the unlabeled MSCs. Additionally, the labeled MSC group showed increased cytokines and reduced pro-inflammatory factors compared with the unlabeled MSC group. The Fe3O4@PDA NPs enhanced stromal cell-derived factor-1/CXCR4-mediated MSC migration in vivo. Thus, we demonstrated the safety, feasibility, and potential efficacy of using the Fe3O4@PDA NPs for optimizing MSC-based therapeutic strategies for burn wound healing.

The photothermal response of nanomaterials provides a basis for many biomedical applications, including diagnosis (e.g., biosensor and photoacoustic imaging) and treatment (e.g., drug delivery and photothermal therapy). The use of nano-materials for cancer phototherapy (solid tumor ablation) can cause cell necrosis and apoptosis. However, photothermal effects using the same material can differ among tumor cell types, and the molecular mechanisms underlying these differences are not clear. We used polydopamine (PDA)-coated branched Au-Ag nanoparticles (Au-Ag@PDA NPs) for the photothermal treatment of two prostate cancer cell lines. The therapeutic effect was evaluated by CCK8, flow cytometry, and expression analyses of related genes by western blotting. Photothermal therapy resulted in oxidative stress in prostate cancer cells and activated the mitochondrial-related apoptosis pathway, increasing the Bax expression. In addition, we observed a greater photothermal treatment effect on the androgen-dependent cells LNCaP than the androgen-independent cells DU145. Pretreatment with an inhibitor of the NF-κB signaling pathway (BAY 11-7082) enhanced the expression of BAX in the DU145 cells and increased the sensitivity of the cells to the heat treatment of Au-Ag@PDA NPs both in vitro and in vivo. Our findings explain the differences in the observed effects of photothermal therapy and provide the direction for further improvements to this strategy.

Meichen Liu,1 Weijia Yu,2 Fuqiang Zhang,2 Te Liu,2 Kai Li,1 Meng Lin,3 Ying Wang,2 Guoqing Zhao,1 Jinlan Jiang2 1Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 2Department of Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 3Department of Breast Surgery, The First Hospital of Jilin University, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Guoqing Zhao; Jinlan Jiang No. 126, Xiantai Street, Changchun City, Jilin Province, People’s Republic of ChinaEmail guoqing@jlu.edu.cn; jiangjinlan@jlu.edu.cnPurpose: Neuropathic pain causes great distress among patients; however, its response to traditional analgesia techniques remains sub-optimal. There has been progress in stem cell research for neuropathic pain treatment; however, effective homing remains problematic. This study aimed to establish Fe3O4@polydopamine(PDA)-labeled mesenchymal stem cells (MSCs); moreover, we aimed to guide MSCs using a magnetic field to the spinal cord segments showing pain-related responses to allow MSC homing and gathering, in advance, in order to fully employ their repair function.Materials and Methods: Fe3O4@PDA-labeled MSCs were characterized using transmission electron microscopy. We analyzed the characteristics of MSCs, as well as the nanoparticle effects on MSC activity, differentiation, and proliferation, using the CCK-8 method, flow cytometry, and staining. Using rats, we performed behavioral tests of mechanical and thermal pain hypersensitivity. Serum inflammatory markers were detected using ELISA. Finally, changes in proteins associated with spinal cord pain were detected through quantitative reverse transcription PCR, histology, and immunohistochemistry.Results: Fe3O4@PDA did not affect the characteristics and viability of MSCs. The magnetic field guidance improved the therapeutic effect of Fe3O4@PDA-labeled MSCs as indicated by the paw withdrawal threshold. Fe3O4@PDA-labeled MSCs decreased spinal nerve demyelination and c-Fos expression (a pain molecule); moreover, they inhibited microglia and astrocyte activation.Conclusion: Fe3O4@PDA-labeled MSCs showed better homing to the spinal cord under magnetic field guidance. Moreover, they inhibited microglial and astrocyte activation, as well as played an early and continuous role in neuropathic pain treatment.Keywords: Fe3O4@PDA, MSCs, neuropathic pain, microglia, astrocytes

Human mesenchymal stem cell (MSC)-derived exosomes (Exos) are a promising therapeutic agent for cell-free regenerative medicine. However, their poor organ-targeting ability and therapeutic efficacy have been found to critically limit their clinical applications. In the present study, we fabricated iron oxide nanoparticle (NP)-labeled exosomes (Exo + NPs) from NP-treated MSCs and evaluated their therapeutic efficacy in a clinically relevant model of skin injury. We found that the Exos could be readily internalized by human umbilical vein endothelial cells (HUVECs), and could significantly promote their proliferation, migration, and angiogenesis both in vitro and in vivo. Moreover, the protein expression of proliferative markers (Cyclin D1 and Cyclin A2), growth factors (VEGFA), and migration-related chemokines (CXCL12) was significantly upregulated after Exo treatment. Unlike the Exos prepared from untreated MSCs, the Exo + NPs contained NPs that acted as a magnet-guided navigation tool. The in vivo systemic injection of Exo + NPs with magnetic guidance significantly increased the number of Exo + NPs that accumulated at the injury site. Furthermore, these accumulated Exo + NPs significantly enhanced endothelial cell proliferation, migration, and angiogenic tubule formation in vivo; moreover, they reduced scar formation and increased CK19, PCNA, and collagen expression in vivo. Collectively, these findings confirm the development of therapeutically efficacious extracellular nanovesicles and demonstrate their feasibility in cutaneous wound repair.

Lian Duan,1 Jianlin Zuo,2 Fuqiang Zhang,1 Binxi Li,3 Zhonghang Xu,4 Hao Zhang,3 Bai Yang,3 Wenzhi Song,5 Jinlan Jiang1 1Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 2Department of Orthopaedics, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 3State Key Laboratory of Supramolecular Structure and Material, College of Chemistry, Jilin University, Changchun, Jilin, People’s Republic of China; 4Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin, People’s Republic of China; 5Department of Stomatology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Jinlan Jiang; Wenzhi SongChina-Japan Union Hospital of Jilin University, No. 126 Xian Tai Street, Changchun, Jilin, People’s Republic of ChinaTel|Fax +86 431-84995432Email jiangjinlan@jlu.edu.cn; songwz@jlu.edu.cnPurpose: Osteonecrosis of the femoral head (ONFH) is a chronic and irreversible disease that eventually develops into a joint collapse and results in joint dysfunction. Early intervention and treatment are essential for preserving the joints and avoiding hip replacement. In this study, a system of human umbilical mesenchymal stem cells-supermagnetic iron oxide nanoparticles (NPs) @polydopamine (SCIOPs) was constructed. The magnetic targeting system gathers in the lesion area, inhibits the apoptosis of bone cells, enhances osteogenic effect, and effectively treats ONFH under external magnetic field.Materials and Methods: The supermagnetic iron oxide NPs @polydopamine (SPION@PDA NPs) were characterized by transmission electron microscopy and zeta potential, respectively. The effects of SPION@PDA NPs on the viability, proliferation, and differentiation of stem cells were detected by the CCK8 method, flow cytometry, and staining, respectively. The serum inflammatory indicators were detected by Luminex method. The bone mass of the femoral head was analyzed by micro computed tomography. The expression of apoptosis and osteoblast-related cytokines was detected by Western blotting. The osteogenesis of the femoral head was detected by histological and immunohistochemical sections.Results: The SCIOPs decreased the pro-inflammatory factors, and the micro CT showed that the bone repair of the femoral head was enhanced after treatment. The hematoxylin and eosin sections also showed an increase in the osteogenesis in the femoral head. Western blotting results showed and increased expression of anti-apoptotic proteins Akt and Bcl-2, decreased expression of apoptotic proteins caspase-3 and Bad, and increased expression of osteogenic proteins Runx-2 and Osterix in the femoral head.Conclusion: Under the effect of magnetic field and homing ability of stem cells, SCIOPs inhibited the apoptosis of osteoblasts, improved the proliferation ability of osteoblasts, and promoted bone repair in the femoral head through the Akt/Bcl-2/Bad/caspase-3 signaling pathway, thereby optimizing the tissue repair ability.Keywords: SPION@PDA NPs, HU-MSCs, GC-ONFH, apoptosis

Background Topical isotretinoin is commonly used to treat acne. However, topical isotretinoin has side effects and can hardly permeate through the stratum corneum, the most important skin barrier. Therefore, this study aimed to demonstrate the efficacy of nanoparticles as stable carriers with great curative effects, low side effects, and strong transdermal ability. Results In a rabbit model of hyperkeratinization, STCM-ATRA-NPs showed significant therapeutic efficacy. By contrast, negative therapeutic efficacy was observed in a golden hamster model of hyper sebum production. Scanning electron microscopy and Fourier transform infrared spectral analyses showed that nanoparticles could penetrate the stratum corneum. Western blotting demonstrated that the nanoparticles could enhance the transdermal efficacy of isotretinoin by reducing the effect of keratin and tight junction proteins. Further, nanoparticles enhanced endocytosis, thereby promoting drug penetration and absorption into the skin. Conclusion STCM-ATRA-NPs were demonstrated to control isotretinoin release, reducing its side effects, and efficiently permeating through the skin by reducing the effect of keratin and tight junction proteins and enhancing endocytosis.

The polydopamine coating on Au-Ag nanoparticles (Au-Ag-PDA) possess excellent photothermal conversion efficiency after absorbing near-infrared laser light. After the stem cell membrane (STCM) encapsulates Au-Ag-PDA (Au-Ag-PDA@STCM), the nanoparticles (NPs) exhibit less cytotoxicity, and further optimizing their efficiency in photothermal therapy. The photothermal activity of Au-Ag-PDA@STCM has not yet been reported. Therefore, in this study, the sebaceous gland cell line SZ95 and the golden hamsters were used to observe the photothermal effects of the Au-Ag-PDA@STCM. SZ95 cells were treated with various concen-trations of Au-Ag-PDA@STCM NPs. The photothermal effect on cell proliferation was analyzed after irradiating the cells with a 808 nm laser. After laser treatment of golden hamsters, the flank organs were observed at 4 different time points. Histological analysis was performed to observe tissue damage. The results suggest that Au-Ag-PDA@STCM NPs significantly inhibited the proliferation of sebaceous gland cells in vitro, and reduced the size of sebaceous glands and sebum secretion in vivo. Therefore, NPs can be used to treat acne by thermally injuring sebaceous gland cells.

Aim: Procaine-derived carbon dots, termed P-dots, expectedly offer both fluorescent biomarker function and anticancer activity. Materials & methods: P-dots were synthesized by condensing procaine, citric acid and ethylenediamine via hydrothermal synthesis and characterized by transmission electron microscopy, Fourier transform infrared spectroscopy and x-ray photoelectron spectroscopy. The cellular uptake behavior and the bioimaging performance of P-dots were assessed by confocal laser scanning microscopy. Their antitumor activity was evaluated using the CCK-8 assays and in vivo antitumor experiments, and the underlying mechanism was evaluated by flow cytometry and western blotting. Results: P-dots exhibited excellent luminescence properties suitable for bioimaging and considerable anticancer activity associated with caspase-3-related cell apoptosis. Conclusion: The synthesized procaine-derived carbon dots presented a dual function consisting of bioimaging and anticancer activity, which may enable their implementation as safe and effective clinical nanotherapeutics.

Hua Yao,1,* Jing Li,1,* Yubin Song,2 Hong Zhao,1 Zhenhong Wei,1 Xiuying Li,1 Yongri Jin,3 Bai Yang,2 Jinlan Jiang1 1Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin, P. R. China; 2State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, Jilin, P. R. China; 3College of Chemistry, Jilin University, Changchun, Jilin, P. R. China *These authors contributed equally to this work Background: Fluorescent carbon-based nanomaterials have promising properties such as biosensing, cell imaging, tracing and drug delivery. However, carbon dots (CDs) with specific inherent biological functions have not been investigated. Ginsenosides are the components with multiple bioactivities found in plants of the genus Panax, which have attracted a lot of attention for their anticancer effect.Materials and methods: In this study, we prepared a kind of novel photoluminescent CDs from ginsenoside Re by one-step hydrothermal synthesis method. The conventional methods including transmission electron microscopy, Fourier transform infrared spectroscopy, HPLC and fluorescence spectrum were used for characterization of CDs. In vitro anticancer effect was investigated by cytotoxicity assay, flow cytometry and Western blot analysis.Results: The as-prepared Re-CDs had an average diameter of 4.6±0.6 nm and excellent luminescent properties. Cellular uptake of Re-CDs was facilitated by their tiny nanosize, with evidence of their bright excitation-dependent fluorescent images. Compared with ginsenoside Re, the Re-CDs showed greater inhibition efficiency of cancer cell proliferation, with lower toxicity to the normal cells. The anticancer activity of Re-CDs was suggested to be associated with the generation of large amount of ROS and the caspase-3 related cell apoptosis.Conclusion: Hopefully, the dual functional Re-CDs, which could both exhibit bioimaging and anticancer effect, are expected to have great potential in future clinical applications. Keywords: carbon dots, ginsenoside Re, excitation-dependent fluorescence, cell imaging, anticancer activity

Biomimetic cell membrane coated nanoparticles (NPs) with desirable features have been extensively applied for various personalized biomedicine. However, there have not been relative explorations by employing the membrane nanocomplexes for small interfering RNA (siRNA) delivery. Herein, Fe3O4@PDA NPs with good photothermal capability were applied for efficient siRNA loading and delivery, which were then coated by mesenchymal stem cells (MSCs) to form a membrane. The data showed that MSCs membrane coated Fe3O4@PDA–siRNA NPs (Fe3O4@PDA–siRNA@MSCs) maintained the photothermal functionality and the capability of magnetic resonance imaging inherited from Fe3O4@PDA. The synthesized nanocomplexes exhibited excellent abilities in the delivery of siRNA into DU145 cells. Furthermore, Fe3O4@PDA–siRNA@MSCs NPs delivering siRNA against Plk1 gene could inhibit the expression of endogenous Plk1 gene and cause obvious apoptosis in DU145 cells. The synergistic combination of photothermal treatment and gene silencing showed...

Gold nanorods (GNRs) have become an attractive candidate in photothermal ablation against cancer cells for their excellent photothermal transduction effect. However, the applications of GNRs in nan...

Au nanorods (AuNRs) have attracted extensive attention in diagnosis and therapy, because of their excellent photothermal effects. Although many of attempts have been employed to prepare AuNRs with a good-size monodispersity, facile and feasible preparation methods are still welcomed in consideration of theranostics-related photothermal applications. In this work, AuNRs are prepared through a seedless method using hydroquinone as the reductant. The longitudinal located surface plasmon resonance peak of the as-prepared AuNRs can be tuned from 650 to 840 nm and the AuNRs indicate a good photothermal conversion efficiency. To lower the toxicity, natural red blood cell membranes are employed to coat the AuNRs. In the primary experiment in vitro, red blood cell membrane-coated AuNRs exhibit good biocompatibility and photothermal treatment effect.

Development of high-performance carbon dots (CDs) with emission wavelength longer than 660 nm (deep red emission) is critical in deep-tissue bioimaging, yet it is still a major challenge to obtain CDs with both narrow full width at half maximum (FWHM) and high deep red/near-infrared emission yield. Here, deep red emissive carbonized polymer dots (CPDs) with unprecedented FWHM of 20 nm are synthesized. The purified CPDs in dimethyl sulfoxide (DMSO) solution possess quantum yield (QY) as high as 59% under 413 nm excitation, as well as recorded QY of 31% under 660 nm excitation in the deep red fluorescent window. Detailed characterizations identify that CPDs have unique polymer characteristics, consisting of carbon cores and the shells of polymer chains, and π conjugated system formed with N heterocycles and aromatic rings governs the single photoluminescence (PL) center, which is responsible for high QY in deep red emissive CPDs with narrow FWHM. The CPDs exhibit strong absorption and emission in the deep red light region, low toxicity, and good biocompatibility, making them an efficient probe for both one-photon and two-photon bioimaging. CPDs are rapidly excreted via the kidney system and hepatobiliary system.

Multifunctional nanocomposites that have multiple therapeutic functions together with real-time imaging capabilities have attracted intensive concerns in the diagnosis and treatment of cancer. This study developed epidermal growth factor receptor (EGFR) antibody-directed polydopamine-coated Fe3O4 nanoparticles (Fe3O4@PDA NPs) for magnetic resonance imaging and antitumor chemo-photothermal therapy. The synthesized Fe3O4@PDA-PEG-EGFR-DOX NPs revealed high storage capacity for doxorubicin (DOX) and high photothermal conversion efficiency. The cell viability assay of Fe3O4@PDA-PEG-EGFR NPs indicated that Fe3O4@ PDA-PEG-EGFR NPs had no cell cytotoxicity. However, Fe3O4@PDA-PEG-EGFR-DOX NPs could significantly decrease cell viability (~5% of remaining cell viability) because of both photothermal ablation and near-infrared light-triggered DOX release. Meanwhile, the EGFR-targeted Fe3O4@PDA-PEG-EGFR-DOX NPs significantly inhibited the growth of tumors, showing a prominent in vivo synergistic antitumor effect. This study demonstrated the potential of using Fe3O4@PDA NPs for combined cancer chemo-photothermal therapy with increased efficacy.

This paper presents a sensitive and fast cellular shear adhesion force measurement method that uses atomic force microscopy (AFM). AFM is used both as a tool for imaging cells on the nano-scale and as a force sensor for the measurement of the shear adhesion force between a cell and the substrate. After cell imaging, the measurement of cellular shear adhesion force is made based on the different positions of the cell on the nano-scale. Moreover, various pushing speeds of probe and various locations of cells were used in experiments to study their influences. It was found that the measurement of cell adhesion in the upper portion of the cell is different from that in the lower portion. This may reveal that cancer cells have high metastasis tendency after culture for 16–20 h, which is significant for preventing metastasis in patients diagnosed with early cancer lesions. Furthermore, the cellular shear adhesion forces of two types of living cancer cell were obtained based on the measurements of AFM cantilever deflections in the torsional and vertical directions. The results demonstrate that the shear adhesion force of cancer cells is twice as much as that of the same type of cancer cells with tumor-necrosis-factor-related apoptosis-inducing ligand. The proposed method can also be used to measure the cellular shear adhesion force between a cell and the substrate, and for the simultaneous exploration of cells using AFM imaging and manipulation.

Carbon nanoparticles (C-NPs) are novel and competitive luminescent materials both in academic research and practical applications owing to their environment-friendly behavior and high abundance on Earth. Despite the successes in preparing strongly luminescent C-NPs, preserving the luminescence in solid materials is still challenging. With the aim to produce C-NP-based white-light-emitting diodes (WLEDs), in this work, solvent-dispersible C-NPs are embedded into commercial silica gel via a dual solvent evaporation route. The basic idea is to lower the evaporation rate of the solvents, thus leading to a good dispersion of the C-NPs in the silica gel. This method avoids the aggregation-induced emission quenching of C-NPs in solid materials, and therefore preserves the strong luminescence in the C-NPs/silica gel composites. The composites are further blended with polydimethylsiloxane and act as the color conversion layer on InGaN UV-blue emitting chips, which produces LEDs with a bright white emission.

Xiuying Li,1,* Zhenhong Wei,1,* Huiying Lv,1 Liya Wu,1 Yingnan Cui,1 Hua Yao,1 Jing Li,1 Hao Zhang,2 Bai Yang,2 Jinlan Jiang1 1Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 2State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, Jilin, People’s Republic of China *These authors contributed equally to this work Background: Developing new methods to deliver cells to the injured tissue is a critical factor in translating cell therapeutics research into clinical use; therefore, there is a need for improved cell homing capabilities. Materials and methods: In this study, we demonstrated the effects of labeling rat bone marrow-derived mesenchymal stem cells (MSCs) with fabricated polydopamine (PDA)-capped Fe3O4 (Fe3O4@PDA) superparticles employing preassembled Fe3O4 nanoparticles as the cores. Results: We found that the Fe3O4@PDA composite superparticles exhibited no adverse effects on MSC characteristics. Moreover, iron oxide nanoparticles increased the number of MSCs in the S-phase, their proliferation index and migration ability, and their secretion of vascular endothelial growth factor relative to unlabeled MSCs. Interestingly, nanoparticles not only promoted the expression of C-X-C chemokine receptor 4 but also increased the expression of the migration-related proteins c-Met and C-C motif chemokine receptor 1, which has not been reported previously. Furthermore, the MSC-loaded nanoparticles exhibited improved homing and anti-inflammatory abilities in the absence of external magnetic fields invivo. Conclusion: These results indicated that iron oxide nanoparticles rendered MSCs more favorable for use in injury treatment with no negative effects on MSC properties, suggesting their potential clinical efficacy. Keywords: mesenchymal stem cells, migration, Fe3O4 nanoparticles, polydopamine

Iron oxide (Fe3O4), polydopamine (PDA), and in particular their composites are examples of the safest nanomaterials for developing multifunctional nanodevices to perform noninvasive tumor diagnosis and therapy. However, the structures and performances of Fe3O4-PDA nanocomposites should be further perfected to enhance the theranostic efficiency. In this work, we demonstrate the fabrication of PDA-capped Fe3O4 (Fe3O4@PDA) superparticles (SPs) employing preassembled Fe3O4 nanoparticles (NPs) as the cores. Owing to the collective effect of preassembled Fe3O4 NPs, the superparamagnetism and photothermal performance of Fe3O4@PDA SPs are greatly enhanced, thus producing nanodevices with improved magnetic resonance imaging (MRI)-guided photothermal efficiency. Systematical studies reveal that the molar extinction coefficient of the as-assembled Fe3O4 SPs is 3 orders of magnitude higher than that of individual Fe3O4 NPs. Also due to the high aggregation degree of Fe3O4 NPs, the T2-weighted MRI contrast is greatly enhanced for the SPs with r2 relaxivity of 230.5 mM(-1) s(-1), which is ∼2.5 times larger than that of individual Fe3O4 NPs. The photothermal stability, physiological stability, and biocompatibility, as well as the photothermal performance of Fe3O4 SPs, are further improved by enveloping with PDA shell.

Xiaoming Zhao,1,* Tianyang Qi,1,* Chenfei Kong,1 Miao Hao,1 Yuqian Wang,1 Jing Li,1 Baocai Liu,2 Yiyao Gao,1 Jinlan Jiang1 1Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, China; 2Department of Radiation Oncology, China-Japan Union Hospital of Jilin University, Changchun, China *These authors contributed equally to this work Purpose: Polydopamine-coated branched Au–Ag nanoparticles (Au–Ag@PDA NPs) exhibit good structural stability, biocompatibility, and photothermal performance, along with potential anticancer efficacy. Here, we investigated the cytotoxicity of Au–Ag@PDA NPs against human bladder cancer cells (T24 cells) in vitro and in vivo, as well as the underlying molecular mechanisms of photothermal therapy-induced T24 cell death.Materials and methods: T24 cells were treated with different doses of Au–Ag@PDA NPs followed by 808 nm laser irradiation, and the effects on cell proliferation, cell cycle, apoptosis, and autophagy were analyzed. To confirm the mechanisms of inhibition, real-time PCR and Western blot analysis were used to evaluate markers of cell cycle, apoptosis, autophagy, and the AKT/ERK signaling pathway. Moreover, we evaluated the effects of the treatment on mitochondrial membrane potential and ROS generation to confirm the underlying mechanisms of inhibition. Finally, we tested the T24 tumor inhibitory effects of Au–Ag@PDA NPs plus laser irradiation in vivo using a xenograft mouse model.Results: Au–Ag@PDA NPs, with appropriate laser irradiation, dramatically inhibited the proliferation of T24 cells, altered the cell cycle distribution by increasing the proportion of cells in the S phase, induced cell apoptosis by activating the mitochondria-mediated intrinsic pathway, and triggered a robust autophagy response in T24 cells. Moreover, Au–Ag@PDA NPs decreased the expression of phosphorylated AKT and ERK and promoted the production of ROS that function upstream of apoptosis and autophagy. In addition, Au–Ag@PDA NP-mediated photothermolysis also significantly suppressed tumor growth in vivo.Conclusion: This preclinical study can provide a mechanistic basis for Au–Ag@PDA NP-mediated photothermal therapy toward promotion of this method in the clinical treatment of bladder cancer. Keywords: nanoparticles, photothermal therapy, near-infrared laser, cell cycle, apoptosis, autophagy

Nanoparticles are emerging as a new therapeutic modality due to their high stability, precise targeting, and high biocompatibility. Branched Au-Ag nanoparticles with polydopamine coating (Au-Ag@PDA) have strong near-infrared absorbance and no cytotoxicity but high photothermal conversion efficiency. However, the photothermal activity of Au-Ag@PDA in vivo and in vitro has not been reported yet, and the mechanism underlying the effects of photothermal nanomaterials is not clear. Therefore, in this study, the colorectal cancer cell line HCT-116 and nude mice xenografts were used to observe the photothermal effects of Au-Ag@PDA in vivo and in vitro. The results suggest that Au-Ag@PDA NPs significantly inhibited cell proliferation and induced apoptosis in colorectal cancer cells. Moreover, Au-Ag@PDA NP-mediated photothermal therapy inhibited the growth of tumors at doses of 50 and 100 μg in vivo. The mechanisms through which Au-Ag@PDA NPs induced colorectal cancer cell death involved multiple pathways, including caspase-dependent and -independent apoptosis, mitochondrial damage, lysosomal membrane permeability, and autophagy. Thus, our findings suggest that Au-Ag@PDA NPs could be used as potential antitumor agents for photothermal ablation of colorectal cancer cells.

This article studies the morphological and mechanical features of multinuclear and mononuclear SW480 colon cancer cells by atomic force microscopy to understand their drug-resistance. The SW480 cells were incubated with the fullerenol concentrations of 1 mg/ml and 2 mg/ml. Morphological and mechanical features including the height, length, width, roughness, adhesion force and Young's modulus of three multinuclear cell groups and three mononuclear cell groups were imaged and analyzed. It was observed that the features of multinuclear cancer cells and mononuclear cancer cells were significantly different after the treatment with fullerenol. The experiment results indicated that the mononuclear SW480 cells were more sensitive to fullerenol than the multinuclear SW480 cells, and the multinuclear SW480 cells exhibited a stronger drug-resistance than the mononuclear SW480 cells. This work provides a guideline for the treatments of multinuclear and mononuclear cancer cells with drugs.