448 results on '"Xiao, Wenwu"'
Search Results
2. Site-Specific Albumin-Selective Ligation to Human Serum Albumin under Physiological Conditions
- Author
-
Yu, Xingjian, Ruan, Ming, Wang, Yongheng, Nguyen, Audrey, Xiao, Wenwu, Ajena, Yousif, Solano, Lucas N, Liu, Ruiwu, and Lam, Kit S
- Subjects
Analytical Chemistry ,Biochemistry and Cell Biology ,Chemical Sciences ,Biological Sciences ,Generic health relevance ,Humans ,Serum Albumin ,Human ,Serum Albumin ,Lysine ,Peptide Library ,Peptides ,Protein Binding ,Medicinal and Biomolecular Chemistry ,Organic Chemistry ,Biochemistry and cell biology ,Medicinal and biomolecular chemistry - Abstract
Human serum albumin (HSA) is the most abundant protein in human blood plasma. It plays a critical role in the native transportation of numerous drugs, metabolites, nutrients, and small molecules. HSA has been successfully used clinically as a noncovalent carrier for insulin (e.g., Levemir), GLP-1 (e.g., Liraglutide), and paclitaxel (e.g., Abraxane). Site-specific bioconjugation strategies for HSA only would greatly expand its role as the biocompatible, non-toxic platform for theranostics purposes. Using the enabling one-bead one-compound (OBOC) technology, we generated combinatorial peptide libraries containing myristic acid, a well-known binder to HSA at Sudlow I and II binding pockets, and an acrylamide. We then used HSA as a probe to screen the OBOC myristylated peptide libraries for reactive affinity elements (RAEs) that can specifically and covalently ligate to the lysine residue at the proximity of these pockets. Several RAEs have been identified and confirmed to be able to conjugate to HSA covalently. The conjugation can occur at physiological pH and proceed with a high yield within 1 h at room temperature. Tryptic peptide profiling of derivatized HSA has revealed two lysine residues (K225 and K414) as the conjugation sites, which is much more specific than the conventional lysine labeling strategy with N-hydroxysuccinimide ester. The RAE-driven site-specific ligation to HSA was found to occur even in the presence of other prevalent blood proteins such as immunoglobulin or whole serum. Furthermore, these RAEs are orthogonal to the maleimide-based conjugation strategy for Cys34 of HSA. Together, these attributes make the RAEs the promising leads to further develop in vitro and in vivo HSA bioconjugation strategies for numerous biomedical applications.
- Published
- 2022
3. Nanoradiosensitizer with good tissue penetration and enhances oral cancer radiotherapeutic effect
- Author
-
Jing, Di, Jiang, Nian, Wang, Fengyi, Mao, Chunping, Han, Shujun, Ho, Pui Yan, Xiao, Wenwu, Li, Yuanpei, Li, Jian Jian, Zhang, Lu, and Lam, Kit S
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Digestive Diseases ,Radiation Oncology ,Dental/Oral and Craniofacial Disease ,Orphan Drug ,Cancer ,Rare Diseases ,6.5 Radiotherapy and other non-invasive therapies ,Cell Line ,Tumor ,Disulfides ,Humans ,Micelles ,Mouth Neoplasms ,Paclitaxel ,Tissue Distribution ,Radio-sensitizer ,Nano-micelle ,Radiotherapy ,Oral cancer - Abstract
Low dose non-toxic disulfide cross-linked micelle (DCM) encapsulated paclitaxel (PTX) was found to be highly efficacious as a radiosensitizer against oral cancer preclinical model. Intensity-modulated radiation therapy was locally administered for three consecutive days 24 h after intravascular injection of DCM-[PTX] at 5 mg/kg PTX. DCM-[PTX] NPs combined with conventional radiotherapy (2 Gy) resulted in a 1.7-fold improvement in therapeutic efficacy compared to conventional PTX plus radiotherapy. Interestingly, we found that radiotherapy can decrease tight junctions and increase the accumulation of DCM-[PTX] in tumor sites. Stereotactic body radiotherapy (SBRT) given at 6 Gy was used to further investigate the synergistic anti-tumor effect. Tumor tissues were collected to analyze the relationship between the time interval after SBRT and the biodistribution of the nanomaterials. Compared to combination DCM-[PTX] with conventional radiation dose, combination DCM-PTX with SBRT was found to be more efficacious in inhibiting tumor growth.
- Published
- 2022
4. Programmable Bispecific Nano-immunoengager That Captures T Cells and Reprograms Tumor Microenvironment
- Author
-
Zhang, Lu, Bo, Ruonan, Wu, Yi, Li, Longmeng, Zhu, Zheng, Ma, Ai-Hong, Xiao, Wenwu, Huang, Yanyu, Rojalin, Tatu, Yin, Xingbin, Mao, Chunping, Wang, Fengyi, Wang, Yongheng, Zhang, Hongyong, Low, Kelmen E, Lee, Kiana, Ajena, Yousif, Jing, Di, Zhang, Dalin, Baehr, Christopher M, Liu, Ruiwu, Wang, Lei, Li, Yuanpei, and Lam, Kit S
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Cancer ,Nanotechnology ,Bioengineering ,Animals ,Immunomodulation ,Integrins ,Mice ,Neoplasms ,T-Lymphocytes ,Tumor Microenvironment ,nano-immuno-engager ,fibrillar transformation ,T cells capture ,immune checkpoint blockade (ICB) therapy ,Nanoscience & Nanotechnology - Abstract
Immune checkpoint blockade (ICB) therapy has revolutionized clinical oncology. However, the efficacy of ICB therapy is limited by the ineffective infiltration of T effector (Teff) cells to tumors and the immunosuppressive tumor microenvironment (TME). Here, we report a programmable tumor cells/Teff cells bispecific nano-immunoengager (NIE) that can circumvent these limitations to improve ICB therapy. The peptidic nanoparticles (NIE-NPs) bind tumor cell surface α3β1 integrin and undergo in situ transformation into nanofibrillar network nanofibers (NIE-NFs). The prolonged retained nanofibrillar network at the TME captures Teff cells via the activatable α4β1 integrin ligand and allows sustained release of resiquimod for immunomodulation. This bispecific NIE eliminates syngeneic 4T1 breast cancer and Lewis lung cancer models in mice, when given together with anti-PD-1 antibody. The in vivo structural transformation-based supramolecular bispecific NIE represents an innovative class of programmable receptor-mediated targeted immunotherapeutics to greatly enhance ICB therapy against cancers.
- Published
- 2022
5. Performance improvement of a tunnel junction memristor with amorphous insulator film
- Author
-
Liu, Fenning, Peng, Yue, Liu, Yan, Xiao, Wenwu, Hao, Yue, and Han, Genquan
- Published
- 2023
- Full Text
- View/download PDF
6. Magnetic resonance imaging of tumor-associated-macrophages (TAMs) with a nanoparticle contrast agent
- Author
-
Zhou, Junhan, Meli, Vijaykumar S, Chen, Esther Yu-Tin, Kapre, Rohan, Nagalla, Raji, Xiao, Wenwu, Borowsky, Alexander D, Lam, Kit S, Liu, Wendy F, and Louie, Angelique Y
- Subjects
Chemical Sciences ,Breast Cancer ,Women's Health ,Cancer ,Biomedical Imaging ,Nanotechnology ,Bioengineering ,Chemical sciences - Abstract
In the tumor micro-environment, tumor associated macrophages (TAMs) represent a predominant component of the total tumor mass, and TAMs play a complex and diverse role in cancer pathogenesis with potential for either tumor suppressive, or tumor promoting biology. Thus, understanding macrophage localization and function are essential for cancer diagnosis and treatment. Typically, tissue biopsy is used to evaluate the density and polarization of TAMs, but provides a limited "snapshot" in time of a dynamic and potentially heterogeneous tumor immune microenvironment. Imaging has the potential for three-dimensional mapping; however, there is a paucity of macrophage-targeted contrast agents to specifically detect TAM subtypes. We have previously found that sulfated-dextran coated iron oxide nanoparticles (SDIO) can target macrophage scavenger receptor A (SR-A, also known as CD204). Since CD204 (SR-A) is considered a biomarker for the M2 macrophage polarization, these SDIO might provide M2-specific imaging probes for MRI. In this work, we investigate whether SDIO can label M2-polarized cells in vitro. We evaluate the effect of degree of sulfation on uptake by primary cultured bone marrow derived macrophages (BMDM) and found that a higher degree of sulfation led to higher uptake, but there were no differences across the subtypes. Further analysis of the BMDM showed similar SR-A expression across stimulation conditions, suggesting that this classic model for macrophage subtypes may not be ideal for definitive M2 subtype marker expression, especially SR-A. We further examine the localization of SDIO in TAMs in vivo, in the mammary fat pad mouse model of breast cancer. We demonstrate that uptake by TAMs expressing SR-A scales with degree of sulfation, consistent with the in vitro studies. The TAMs demonstrate M2-like function and secrete Arg-1 but not iNOS. Uptake by these M2-like TAMs is validated by immunohistochemistry. SDIO show promise as a valuable addition to the toolkit of imaging probes targeted to different biomarkers for TAMs.
- Published
- 2022
7. Fatty acid oxidation fuels glioblastoma radioresistance with CD47-mediated immune evasion
- Author
-
Jiang, Nian, Xie, Bowen, Xiao, Wenwu, Fan, Ming, Xu, Shanxiu, Duan, Yixin, Hamsafar, Yamah, Evans, Angela C, Huang, Jie, Zhou, Weibing, Lin, Xuelei, Ye, Ningrong, Wanggou, Siyi, Chen, Wen, Jing, Di, Fragoso, Ruben C, Dugger, Brittany N, Wilson, Paul F, Coleman, Matthew A, Xia, Shuli, Li, Xuejun, Sun, Lun-Quan, Monjazeb, Arta M, Wang, Aijun, Murphy, William J, Kung, Hsing-Jien, Lam, Kit S, Chen, Hong-Wu, and Li, Jian Jian
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Brain Cancer ,Rare Diseases ,Cancer ,Brain Disorders ,Neurosciences ,Animals ,CD47 Antigen ,Cell Line ,Tumor ,Fatty Acids ,Glioblastoma ,Humans ,Immune Evasion ,Mice ,Phagocytosis - Abstract
Glioblastoma multiforme (GBM) remains the top challenge to radiotherapy with only 25% one-year survival after diagnosis. Here, we reveal that co-enhancement of mitochondrial fatty acid oxidation (FAO) enzymes (CPT1A, CPT2 and ACAD9) and immune checkpoint CD47 is dominant in recurrent GBM patients with poor prognosis. A glycolysis-to-FAO metabolic rewiring is associated with CD47 anti-phagocytosis in radioresistant GBM cells and regrown GBM after radiation in syngeneic mice. Inhibition of FAO by CPT1 inhibitor etomoxir or CRISPR-generated CPT1A-/-, CPT2-/-, ACAD9-/- cells demonstrate that FAO-derived acetyl-CoA upregulates CD47 transcription via NF-κB/RelA acetylation. Blocking FAO impairs tumor growth and reduces CD47 anti-phagocytosis. Etomoxir combined with anti-CD47 antibody synergizes radiation control of regrown tumors with boosted macrophage phagocytosis. These results demonstrate that enhanced fat acid metabolism promotes aggressive growth of GBM with CD47-mediated immune evasion. The FAO-CD47 axis may be targeted to improve GBM control by eliminating the radioresistant phagocytosis-proofing tumor cells in GBM radioimmunotherapy.
- Published
- 2022
8. Transformable amyloid-beta mimetic peptide amphiphiles for lysosomal disruption in non-small cell lung cancer
- Author
-
Baehr, Christopher M, Zhang, Lu, Wu, Yi, Domokos, Andras, Xiao, Wenwu, Wang, Lei, and Lam, Kit S
- Subjects
Medical Biotechnology ,Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Lung Cancer ,Bioengineering ,Biotechnology ,Nanotechnology ,Lung ,Cancer ,5.1 Pharmaceuticals ,Amyloid beta-Peptides ,Animals ,Carcinoma ,Non-Small-Cell Lung ,Cell Line ,Tumor ,Cisplatin ,Lung Neoplasms ,Lysosomes ,Mice ,Nanoparticles ,Nanofibers ,Non-small cell lung cancer ,Amyloid-beta ,Lysosomal targeting - Abstract
Non-small cell lung cancer (NSCLC) is the largest contributor to cancer mortality in the United States. Traditional chemotherapies are toxic and prone to the development of drug-resistance. Recently, several drug candidates were shown to induce lysosomal membrane permeabilization (LMP) in aggressive cancers. This has led to increased interest in lysosome dysregulation as a therapeutic target. However, approaches are needed to overcome two limitations of current lysosomal inhibitors: low specificity and potency. Here, we report the development of a transformable nanomaterial which is triggered to induce LMP of lysosomes in NSCLC. The nanomaterial consists of peptide amphiphiles, which self-assemble into nanoparticles, colocalize with the lysosome, and change conformation to nanofibrils due to lysosomal pH shift, which leads to the disruption of the lysosome, cell death, and cisplatin sensitization. We have found that this cell-penetrating transformable peptide nanoparticle (CPTNP) was cytotoxic to NSCLC cells in the low-micromolar range and it synergized cisplatin cytotoxicity four-fold. Moreover, we demonstrate CPTNP's promising antitumor effect in mouse xenograft models with limited toxicity when given in combination with low dose cisplatin chemotherapy. This is the first example of enhanced LMP via transformable peptide nanomaterial and offers a promising new strategy for cancer therapy.
- Published
- 2021
9. Rapid discovery of self-assembling peptides with one-bead one-compound peptide library.
- Author
-
Yang, Pei-Pei, Li, Yi-Jing, Cao, Yan, Zhang, Lu, Wang, Jia-Qi, Lai, Ziwei, Zhang, Kuo, Shorty, Diedra, Xiao, Wenwu, Cao, Hui, Wang, Lei, Wang, Hao, Liu, Ruiwu, and Lam, Kit S
- Subjects
Hela Cells ,Humans ,Peptides ,Peptide Library ,Microscopy ,Electron ,Transmission ,X-Ray Diffraction ,Spectroscopy ,Fourier Transform Infrared ,Circular Dichroism ,Combinatorial Chemistry Techniques ,Hydrogen Bonding ,Nanostructures ,Nanofibers ,High-Throughput Screening Assays ,HeLa Cells - Abstract
Self-assembling peptides have shown tremendous potential in the fields of material sciences, nanoscience, and medicine. Because of the vast combinatorial space of even short peptides, identification of self-assembling sequences remains a challenge. Herein, we develop an experimental method to rapidly screen a huge array of peptide sequences for self-assembling property, using the one-bead one-compound (OBOC) combinatorial library method. In this approach, peptides on beads are N-terminally capped with nitro-1,2,3-benzoxadiazole, a hydrophobicity-sensitive fluorescence molecule. Beads displaying self-assembling peptides would fluoresce under aqueous environment. Using this approach, we identify eight pentapeptides, all of which are able to self-assemble into nanoparticles or nanofibers. Some of them are able to interact with and are taken up efficiently by HeLa cells. Intracellular distribution varied among these non-toxic peptidic nanoparticles. This simple screening strategy has enabled rapid identification of self-assembling peptides suitable for the development of nanostructures for various biomedical and material applications.
- Published
- 2021
10. LHRH‐Targeted Redox‐Responsive Crosslinked Micelles Impart Selective Drug Delivery and Effective Chemotherapy in Triple‐Negative Breast Cancer
- Author
-
Xiao, Kai, Liu, Qiangqiang, Suby, Nell, Xiao, Wenwu, Agrawal, Rinki, Vu, Michael, Zhang, Hongyong, Luo, Yan, Li, Yuanpei, and Lam, Kit S
- Subjects
Medical Biotechnology ,Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Breast Cancer ,5.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,Animals ,Cell Line ,Tumor ,Drug Carriers ,Drug Delivery Systems ,Gonadotropin-Releasing Hormone ,Humans ,Micelles ,Oxidation-Reduction ,Paclitaxel ,Polyethylene Glycols ,Triple Negative Breast Neoplasms ,Tumor Microenvironment ,Xenograft Model Antitumor Assays ,breast cancer ,disulfide crosslinkers ,LHRH ,micelles ,paclitaxel ,redox‐ ,responsive micelles ,targeted delivery ,redox-responsive micelles ,Medicinal and Biomolecular Chemistry ,Biomedical Engineering ,Medical biotechnology ,Biomedical engineering - Abstract
Systemic chemotherapy is efficacious against triple-negative breast cancer (TNBC), but it is often associated with serious side effects. Here, a luteinizing hormone-releasing hormone (LHRH) receptor-targeted and tumor microenvironment-responsive nanoparticle system to selectively deliver chemotherapeutic drugs to TNBC cells, is reported. This delivery system (termed "LHRH-DCMs") contains poly(ethylene glycol) and dendritic cholic acid as a micellar carrier, reversible intra-micellar disulfide bond as a redox-responsive crosslink, and synthetic high-affinity (D-Lys)-LHRH peptide as a targeting moiety. LHRH-DCMs exhibit high drug loading efficiency, optimal particle size, good colloidal stability, and glutathione-responsive drug release. As expected, LHRH-DCMs are more efficiently internalized into human TNBC cells through receptor-mediated endocytosis, resulting in stronger cytotoxicity against these cancer cells than the non-targeted counterpart when encapsulated with paclitaxel (PTX). Furthermore, near-infrared fluorescence and magnetic resonance imaging demonstrate that LHRH-DCMs facilitate the tumor distribution and penetration of payloads in three different animal models of breast cancer, including cell line-derived xenograft (CDX), patient-derived xenograft (PDX), and transgenic mammary carcinoma. Finally, in vivo therapeutic studies show that PTX-LHRH-DCMs outperform both the corresponding nontargeted PTX-DCMs and the current clinical formulation (Taxol) in an orthotopic TNBC model. These results provide new insights into approaches for precise drug delivery of TNBC.
- Published
- 2021
11. Impact of polarization switching on the effective carrier mobility of HfZrOx ferroelectric field-effect transistor
- Author
-
Liu, Fenning, Peng, Yue, Xiao, Wenwu, Liu, Yan, Yu, Xiao, and Han, Genquan
- Published
- 2023
- Full Text
- View/download PDF
12. Discovery and mechanistic characterization of a structurally-unique membrane active peptide
- Author
-
Bansal, Shivani, Su, Wan-Chih, Budamagunta, Madhu, Xiao, Wenwu, Ajena, Yousif, Liu, Ruiwu, Voss, John C, Carney, Randy P, Parikh, Atul N, and Lam, Kit S
- Subjects
Biochemistry and Cell Biology ,Biological Sciences ,Bioengineering ,Generic health relevance ,Animals ,Drug Discovery ,Electron Spin Resonance Spectroscopy ,Membrane Proteins ,Mice ,Mice ,Inbred BALB C ,Microscopy ,Fluorescence ,Peptides ,Protein Conformation ,Combinatorial library ,Membrane active peptide ,Giant unilamellar vesicles ,Membrane dynamics ,Interfacial activity ,Membrane activity ,Other Biological Sciences ,Chemical Engineering ,Biochemistry & Molecular Biology ,Biophysics ,Biochemistry and cell biology - Abstract
Membrane active peptides (MAPs) have gained wide interest due to their far reaching applications in drug discovery and drug delivery. The search for new MAPs, however, has been largely skewed with bias selecting for physicochemical parameters believed to be important for membrane activity, such as alpha helicity, cationicity and hydrophobicity. Here we carry out a search-and-find strategy to screen a 100,000-membered one-bead-one-compound (OBOC) combinatorial peptide library for lead compounds, agnostic of those physicochemical constraints. Such a synthetic strategy also permits expansion of our peptide repertoire to include unnatural amino acids. Using this approach, we discovered a structurally unique lead peptide LBF14, a linear 14-mer peptide, that induces gross morphological disruption of membranes, irrespective of membrane composition. Further, we demonstrate that the unique insertion mechanism of the peptide, visualized by spinning disc confocal microscopy and further analyzed by electron paramagnetic resonance measurements, may be the cause of this large scale membrane deformation. We also demonstrate the robustness, reproducibility, and potential application of this technique to discover and characterize new membrane active peptides that display activity by local insertion and subsequent allosteric effects leading to global membrane disruption.
- Published
- 2020
13. A nephrotoxicity-free, iron-based contrast agent for magnetic resonance imaging of tumors
- Author
-
Xue, Xiangdong, Bo, Ruonan, Qu, Haijing, Jia, Bei, Xiao, Wenwu, Yuan, Ye, Vapniarsky, Natalia, Lindstrom, Aaron, Wu, Hao, Zhang, Dalin, Li, Longmeng, Ricci, Marina, Ma, Zhao, Zhu, Zheng, Lin, Tzu-Yin, Louie, Angelique Y, and Li, Yuanpei
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Bioengineering ,Brain Cancer ,Neurosciences ,Biomedical Imaging ,Kidney Disease ,Cancer ,Nanotechnology ,Rare Diseases ,Brain Disorders ,4.1 Discovery and preclinical testing of markers and technologies ,4.2 Evaluation of markers and technologies ,Animals ,Contrast Media ,Gadolinium ,Humans ,Iron ,Magnetic Resonance Imaging ,Mice ,Neoplasms ,Renal Insufficiency ,Nanoparticle ,Contrast agents ,Magnetic resonance imaging ,Tumor imaging ,Nephrotoxicity-free - Abstract
Gadolinium-based contrast agents (GBCAs) are the most widely used T1 contrast agents for magnetic resonance imaging (MRI) and have achieved remarkable success in clinical cancer diagnosis. However, GBCAs could cause severe nephrogenic systemic fibrosis to patients with renal insufficiency. Nevertheless, GBCAs are quickly excreted from the kidneys, which shortens their imaging window and prevents long-term monitoring of the disease per injection. Herein, a nephrotoxicity-free T1 MRI contrast agent is developed by coordinating ferric iron into a telodendritic, micellar nanostructure. This new nano-enabled, iron-based contrast agent (nIBCA) not only can reduce the renal accumulation and relieve the kidney burden, but also exhibit a significantly higher tumor to noise ratio (TNR) for cancer diagnosis. In comparison with Magnevist (a clinical-used GBCA), Magnevist induces obvious nephrotoxicity while nIBCA does not, indicating that such a novel contrast agent may be applicable to renally compromised patients requiring a contrast-enhanced MRI. The nIBCA could precisely image subcutaneous brain tumors in a mouse model and the effective imaging window lasted for at least 24 h. The nIBCA also precisely highlights the intracranial brain tumor with high TNR. The nIBCA presents a potential alternative to GBCAs as it has superior biocompatibility, high TNR and effective imaging window.
- Published
- 2020
14. Identification of osteogenic progenitor cell-targeted peptides that augment bone formation.
- Author
-
Jiang, Min, Liu, Ruiwu, Liu, Lixian, Kot, Alexander, Liu, Xueping, Xiao, Wenwu, Jia, Junjing, Li, Yuanpei, Lam, Kit S, and Yao, Wei
- Subjects
Cells ,Cultured ,Stem Cells ,Mesenchymal Stem Cells ,Animals ,Mice ,Inbred C57BL ,Mice ,Transgenic ,Humans ,Peptides ,Anabolic Agents ,Orchiectomy ,Ovariectomy ,Cell Differentiation ,Calcification ,Physiologic ,Osteogenesis ,Female ,Male ,Fractures ,Bone ,Proto-Oncogene Proteins c-akt ,Solid-Phase Synthesis Techniques ,Regenerative Medicine ,Stem Cell Research ,Osteoporosis ,Stem Cell Research - Nonembryonic - Non-Human ,Underpinning research ,5.1 Pharmaceuticals ,1.1 Normal biological development and functioning ,Development of treatments and therapeutic interventions ,5.2 Cellular and gene therapies ,Musculoskeletal - Abstract
Activation and migration of endogenous mesenchymal stromal cells (MSCs) are critical for bone regeneration. Here, we report a combinational peptide screening strategy for rapid discovery of ligands that not only bind strongly to osteogenic progenitor cells (OPCs) but also stimulate osteogenic cell Akt signaling in those OPCs. Two lead compounds are discovered, YLL3 and YLL8, both of which increase osteoprogenitor osteogenic differentiation in vitro. When given to normal or osteopenic mice, the compounds increase mineral apposition rate, bone formation, bone mass, and bone strength, as well as expedite fracture repair through stimulated endogenous osteogenesis. When covalently conjugated to alendronate, YLLs acquire an additional function resulting in a "tri-functional" compound that: (i) binds to OPCs, (ii) targets bone, and (iii) induces "pro-survival" signal. These bone-targeted, osteogenic peptides are well suited for current tissue-specific therapeutic paradigms to augment the endogenous osteogenic cells for bone regeneration and the treatment of bone loss.
- Published
- 2020
15. Rapid endothelialization of small diameter vascular grafts by a bioactive integrin-binding ligand specifically targeting endothelial progenitor cells and endothelial cells
- Author
-
Hao, Dake, Fan, Yahan, Xiao, Wenwu, Liu, Ruiwu, Pivetti, Christopher, Walimbe, Tanaya, Guo, Fuzheng, Zhang, Xinke, Farmer, Diana L, Wang, Fengshan, Panitch, Alyssa, Lam, Kit S, and Wang, Aijun
- Subjects
Engineering ,Chemical Sciences ,Biomedical Engineering ,Regenerative Medicine ,Atherosclerosis ,Biotechnology ,Assistive Technology ,Hematology ,Stem Cell Research ,Bioengineering ,Cardiovascular ,1.1 Normal biological development and functioning ,Animals ,Blood Vessel Prosthesis ,Endothelial Progenitor Cells ,Endothelium ,Vascular ,Integrins ,Ligands ,Rats ,Vascular Grafting ,Integrin-binding functional ligand ,Platelet suppression ,Rapid endothelialization ,Anti-thrombosis ,Vascular graft - Abstract
Establishing and maintaining a healthy endothelium on vascular and intravascular devices is crucial for the prevention of thrombosis and stenosis. Generating a biofunctional surface on vascular devices to recruit endothelial progenitor cells (EPCs) and endothelial cells (ECs) has proven efficient in promoting in situ endothelialization. However, molecules conventionally used for EPC/EC capturing generally lack structural stability, capturing specificity, and biological functionalities, which have limited their applications. Discovery of effective, specific, and structurally stable EPC/EC capturing ligands is desperately needed. Using the high-throughput One-Bead One-Compound combinatorial library screening technology, we recently identified a disulfide cyclic octa-peptide LXW7 (cGRGDdvc), which possesses strong binding affinity and functionality to EPCs/ECs, weak binding to platelets, and no binding to inflammatory cells. Because LXW7 is cyclic and 4 out of the 8 amino acids are unnatural D-amino acids, LXW7 is highly proteolytically stable. In this study, we applied LXW7 to modify small diameter vascular grafts using a Click chemistry approach. In vitro studies demonstrated that LXW7-modified grafts significantly improved EPC attachment, proliferation and endothelial differentiation and suppressed platelet attachment. In a rat carotid artery bypass model, LXW7 modification of the small diameter vascular grafts significantly promoted EPC/EC recruitment and rapidly achieved endothelialization. At 6 weeks after implantation, LXW7-modified grafts retained a high patency of 83%, while the untreated grafts had a low patency of 17%. Our results demonstrate that LXW7 is a potent EPC/EC capturing and platelet suppressing ligand and LXW7-modified vascular grafts rapidly generate a healthy and stable endothelial interface between the graft surface and the circulation to reduce thrombosis and improve patency. STATEMENT OF SIGNIFICANCE: In this study, One-Bead One-Compound (OBOC) technology has been applied for the first time in discovering bioactive ligands for tissue regeneration applications. Current molecules used to modify artificial vascular grafts generally lack EPC/EC capturing specificity, biological functionalities and structural stability. Using OBOC technology, we identified LXW7, a constitutionally stable disulfide cyclic octa-peptide with strong binding affinity and biological functionality to EPCs/ECs, very weak binding to platelets and no binding to inflammatory cells. These characteristics are crucial for promoting rapid endothelialization to prevent thrombosis and improve patency of vascular grafts. LXW7 coating technology could be applied to a wide range of vascular and intravascular devices, including grafts, stents, cardiac valves, and catheters, where a "living" endothelium and healthy blood interface are needed.
- Published
- 2020
16. Structure-Activity Relationship of RGD-Containing Cyclic Octapeptide and αvβ3 Integrin Allows for Rapid Identification of a New Peptide Antagonist.
- Author
-
Silva, Aaron, Xiao, Wenwu, Wang, Yan, Wang, Wei, Chang, Heng Wei, Ames, James B, Lam, Kit S, and Zhang, Yonghong
- Subjects
RGD peptides ,in silico screening ,in vitro binding ,integrin αvβ3 antagonists ,structure–activity relationship ,integrin alpha v beta 3 antagonists ,structure-activity relationship ,Chemical Physics ,Other Chemical Sciences ,Genetics ,Other Biological Sciences - Abstract
The αvβ3 integrin, a receptor for many extracellular matrix proteins with RGD-sequence motif, is involved in multiple physiological processes and highly expressed in tumor cells, therefore making it a target for cancer therapy and tumor imaging. Several RGD-containing cyclic octapeptide (named LXW analogs) were screened as αvβ3 antagonists with dramatically different binding affinity, and their structure-activity relationship (SAR) remains elusive. We performed systematic SAR studies and optimized LXW analogs to improve antagonistic potency. The NMR structure of LXW64 was determined and docked to the integrin. Structural comparison and docking studies suggested that the hydrophobicity and aromaticity of the X7 amino acid are highly important for LXW analogs binding to the integrin, a potential hydrophobic pocket on the integrin surface was proposed to play a role in stabilizing the peptide binding. To develop a cost-efficient and fast screening method, computational docking was performed on LXW analogs and compared with in vitro screening. A consistency within the results of both methods was found, leading to the continuous optimization and testing of LXW mutants via in silico screening. Several new LXW analogs were predicted as the integrin antagonists, one of which-LXZ2-was validated by in vitro examination. Our study provides new insight into the RGD recognition specificity and valuable clues for rational design of novel αvβ3 antagonists.
- Published
- 2020
17. Sequential Targeting in Crosslinking Nanotheranostics for Tackling the Multibarriers of Brain Tumors
- Author
-
Wu, Hao, Lu, Hongwei, Xiao, Wenwu, Yang, Jinfan, Du, Hongxu, Shen, Yingbin, Qu, Haijing, Jia, Bei, Manna, Suman K, Ramachandran, Mythili, Xue, Xiangdong, Ma, Zhao, Xu, Xiaobao, Wang, Zhongling, He, Yixuan, Lam, Kit S, Zawadzki, Robert J, Li, Yuanpei, and Lin, Tzu‐Yin
- Subjects
Engineering ,Chemical Sciences ,Physical Sciences ,Cancer ,Brain Disorders ,Bioengineering ,Nanotechnology ,Neurosciences ,Brain Cancer ,Orphan Drug ,Rare Diseases ,5.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,Animals ,Antineoplastic Agents ,Blood-Brain Barrier ,Boronic Acids ,Brain ,Brain Neoplasms ,Carbocyanines ,Cell Line ,Tumor ,Disaccharides ,Drug Carriers ,Gadolinium DTPA ,Glioma ,Humans ,Hydrogen-Ion Concentration ,Kaplan-Meier Estimate ,Mice ,Mice ,Inbred BALB C ,Nanoparticles ,Transcytosis ,Xenograft Model Antitumor Assays ,blood-brain barrier ,diffuse intrinsic pontine glioma ,pH response ,sequential targeting ,Nanoscience & Nanotechnology ,Chemical sciences ,Physical sciences - Abstract
The efficacy of therapeutics for brain tumors is seriously hampered by multiple barriers to drug delivery, including severe destabilizing effects in the blood circulation, the blood-brain barrier/blood-brain tumor barrier (BBB/BBTB), and limited tumor uptake. Here, a sequential targeting in crosslinking (STICK) nanodelivery strategy is presented to circumvent these important physiological barriers to improve drug delivery to brain tumors. STICK nanoparticles (STICK-NPs) can sequentially target BBB/BBTB and brain tumor cells with surface maltobionic acid (MA) and 4-carboxyphenylboronic acid (CBA), respectively, and simultaneously enhance nanoparticle stability with pH-responsive crosslinkages formed by MA and CBA in situ. STICK-NPs exhibit prolonged circulation time (17-fold higher area under curve) than the free agent, allowing increased opportunities to transpass the BBB/BBTB via glucose-transporter-mediated transcytosis by MA. The tumor acidic environment then triggers the transformation of the STICK-NPs into smaller nanoparticles and reveals a secondary CBA targeting moiety for deep tumor penetration and enhanced uptake in tumor cells. STICK-NPs significantly inhibit tumor growth and prolong the survival time with limited toxicity in mice with aggressive and chemoresistant diffuse intrinsic pontine glioma. This formulation tackles multiple physiological barriers on-demand with a simple and smart STICK design. Therefore, these features allow STICK-NPs to unleash the potential of brain tumor therapeutics to improve their treatment efficacy.
- Published
- 2020
18. Transformable peptide nanoparticles arrest HER2 signalling and cause cancer cell death in vivo
- Author
-
Zhang, Lu, Jing, Di, Jiang, Nian, Rojalin, Tatu, Baehr, Christopher M, Zhang, Dalin, Xiao, Wenwu, Wu, Yi, Cong, Zhaoqing, Li, Jian Jian, Li, Yuanpei, Wang, Lei, and Lam, Kit S
- Subjects
Biochemistry and Cell Biology ,Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Biological Sciences ,Cancer ,Breast Cancer ,Animals ,Antineoplastic Agents ,Apoptosis ,Breast Neoplasms ,Cell Line ,Tumor ,Female ,Humans ,Mice ,Nanoparticles ,Peptides ,Receptor ,ErbB-2 ,Signal Transduction ,Xenograft Model Antitumor Assays ,Receptor ,erbB-2 ,Nanoscience & Nanotechnology - Abstract
Human epidermal growth factor receptor 2 (HER2) is overexpressed in >20% of breast cancers. Dimerization of HER2 receptors leads to the activation of downstream signals enabling the proliferation and survival of malignant phenotypes. Owing to the high expression levels of HER2, combination therapies are currently required for the treatment of HER2+ breast cancer. Here, we designed non-toxic transformable peptides that self-assemble into micelles under aqueous conditions but, on binding to HER2 on cancer cells, transform into nanofibrils that disrupt HER2 dimerization and subsequent downstream signalling events leading to apoptosis of cancer cells. The phase transformation of peptides enables specific HER2 targeting, and inhibition of HER2 dimerization blocks the expression of proliferation and survival genes in the nucleus. We demonstrate, in mouse xenofraft models, that these transformable peptides can be used as a monotherapy in the treatment of HER2+ breast cancer.
- Published
- 2020
19. High-affinity peptide ligand LXY30 for targeting α3β1 integrin in non-small cell lung cancer
- Author
-
Xiao, Wenwu, Ma, Weijie, Wei, Sixi, Li, Qianping, Liu, Ruiwu, Carney, Randy P, Yang, Kevin, Lee, Joyce, Nyugen, Alan, Yoneda, Ken Y, Lam, Kit S, and Li, Tianhong
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Biotechnology ,Cancer ,Lung ,Lung Cancer ,Clinical Research ,Bioengineering ,Genetics ,4.1 Discovery and preclinical testing of markers and technologies ,5.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,Detection ,screening and diagnosis ,Animals ,Carcinoma ,Non-Small-Cell Lung ,Disease Models ,Animal ,Female ,Humans ,Integrin alpha3beta1 ,Ligands ,Lung Neoplasms ,Mice ,Mice ,Nude ,Peptides ,Cancer-targeting peptide ,integrin ,Non-small cell lung cancer ,Exosomes ,In vivo imaging ,Patient-derived xenograft ,α3β1 integrin ,Cardiorespiratory Medicine and Haematology ,Cardiovascular medicine and haematology ,Oncology and carcinogenesis - Abstract
Backgroundα3β1 integrin is a promising cancer biomarker and drug target. We previously identified a 9-amino-acid cyclic peptide LXY30 for detecting α3β1 integrin on the surface of live tumor cells. This study was undertaken to characterize LXY30 in the detection, cellular function, imaging, and targeted delivery of in vitro and in vivo non-small cell lung cancer (NSCLC) models.MethodsThe whole-cell binding assay was performed by incubating NSCLC cells, extracellular vesicles (EVs), and peripheral blood mononuclear cells (PBMCs) with TentaGel resin beads coated with LXY30. In this study, we defined the nanosize EVs as exosomes, which were characterized by flow cytometry, transmission electron microscopy, dynamic light scattering, and Western blots. The function of LXY30 was determined by modulating the epidermal growth factor receptor (EGFR) signaling pathway by growth inhibition and Western blots. For in vivo biodistribution, mice bearing subcutaneous and intracranial NSCLC xenograft tumors were administrated intraveneously with LXY30-biotin/streptavidin-Cy5.5 complex and then analyzed for in vivo and ex vivo optical imaging and histopathology.ResultsWe showed that LXY30 specifically and sensitively detected α3β1 integrin-expressing NSCLC cells and tumor-derived exosomes. Tumor DNA isolated from LXY30-enriched plasma exosomes might be used to detect driver oncogenic mutations in patients with metastatic NSCLC. LXY30 only enriches tumor cells but not neutrophils, macrophages, or monocytes in the malignant pleural effusion of NSCLC patients for detecting genomic alterations by next-generation sequencing. LXY30 detected increased α3β1 integrin expression on the EGFR-mutant NSCLC cells with acquired resistance to erlotinib compared to parental erlotinib-sensitive EGFR-mutant NSCLC cells. We further showed that LXY30 modulated the EGFR signaling pathway independently from another peptide ligand LXW64 targeting αvβ3 integrin in erlotinib-resistant, EGFR-mutant H1975 cells. Analysis of The Cancer Genome Atlas (TCGA) revealed high α3 integrin expression was associated with poor prognosis in lung squamous cell carcinoma. LXY30-biotin/streptavidin-Cy5.5 complex had higher uptakes in the subcutaneous and intracranial xenografts of various α3β1 integrin-expressing lung adenocarcinoma and patient-derived lung squamous cell carcinoma xenografts while sparing the surrounding normal tissues.ConclusionLXY30 is a promising peptide for the cancer diagnosis and in vivo targeted delivery of imaging agents and cancer drugs in NSCLC, independent of histology and tumor genotype.
- Published
- 2019
20. Correction to: High-affinity peptide ligand LXY30 for targeting α3β1 integrin in non-small cell lung cancer
- Author
-
Xiao, Wenwu, Ma, Weijie, Wei, Sixi, Li, Qianping, Liu, Ruiwu, Carney, Randy P, Yang, Kevin, Lee, Joyce, Nyugen, Alan, Yoneda, Ken Y, Lam, Kit S, and Li, Tianhong
- Subjects
Cancer ,Cardiorespiratory Medicine and Haematology ,Oncology and Carcinogenesis - Abstract
The original article [1] contains an error in Fig. 2 whereby Fig. 2D has mistakenly been omitted. Fig. 2 can be viewed in its entirety - including Fig. 2D - in this Correction article.
- Published
- 2019
21. Hf0.5Zr0.5O2 1T−1C FeRAM arrays with excellent endurance performance for embedded memory
- Author
-
Xiao, Wenwu, Peng, Yue, Liu, Yan, Duan, Huifu, Bai, Fujun, Yu, Bing, Ren, Qiwei, Yu, Xiao, and Han, Genquan
- Published
- 2023
- Full Text
- View/download PDF
22. Effect of electrical stress on time dependent dielectric breakdown (TDDB) tolerate capability of HfO2-ZrO2 ferroelectric films with different thicknesses
- Author
-
Peng, Yue, primary, Wang, Zhe, additional, Wu, Qiuxia, additional, Zhang, Shuo, additional, Ma, Wenxuan, additional, Xiao, Wenwu, additional, Zhang, Chunfu, additional, and Hao, Yue, additional
- Published
- 2024
- Full Text
- View/download PDF
23. The Effect of M-Health-Based Core Stability Exercise Combined with Self-Compassion Training for Patients with Nonspecific Chronic Low Back Pain: A Randomized Controlled Pilot Study
- Author
-
Zheng, Fuming, Zheng, Yiyi, Liu, Shufeng, Yang, Jiajia, Xiao, Weihui, Xiao, Wenwu, Chen, Lichang, Yang, Wanting, Zhang, Shanshan, Yu, Qiuhua, Hao, Zengming, Wang, Yuyin, and Wang, Chuhuai
- Published
- 2022
- Full Text
- View/download PDF
24. One-bead one-compound combinatorial library derived targeting ligands for detection and treatment of oral squamous cancer
- Author
-
Yang, Fan, Xiao, Wenwu, Liu, Yanlei, Liu, Ruiwu, Kramer, Randall, Li, Xiaocen, Ajena, Yousif, Baehr, Christopher M, Rojalin, Tatu, Zhang, Hongyong, and Lam, Kit S
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Digestive Diseases ,Rare Diseases ,Cancer ,Bioengineering ,Prevention ,Dental/Oral and Craniofacial Disease ,5.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,cancer-targeting peptide ,optical imaging ,oral squamous cancer ,orthotopic xenograft model ,α3 integrin ,Oncology and carcinogenesis - Abstract
Oral squamous cancers (OSC) are hallmarked by poor prognosis, delayed clinical detection, and a lack of defined, characteristic biomarkers. By screening combinatorial one-bead one-compound (OBOC) peptide libraries against oral squamous cancer cell lines, two cyclic peptide ligands, LLY12 and LLY13 were previously identified. These ligands are capable of specific binding to the oral cancer cell lines (MOK-101, HSC-3, SCC-4 and SCC-10a) but not non-cancerous keratinocytes, leukocytes, fibroblast, and endothelial cells. These two peptides were synthesized and evaluated for their binding property, cytotoxicity and cell permeability. In vitro studies indicate that both LLY12 and LLY13 were able to bind to oral cancer cells with high specificity but did not show any cytotoxicity against human keratinocytes. Biotinylated LLY13, in complex with streptavidin-alexa488 was taken up by live oral cancer cells, thus rendering it as an excellent candidate vehicle for efficient delivery of drug loaded-nanoparticles. In vivo and ex vivo near infra-red fluorescence imaging studies confirmed the in vivo targeting efficiency and specificity of LLY13 in oral cancer orthotopic murine xenograft model. In vivo studies also showed that LLY13 was able to accumulate in the OSC tumors and demarcate the tumor margins in orthotopic xenograft model. Together, our data supports LLY13 as a promising theranostic agent against OSC.
- Published
- 2019
25. Dual blockage of STAT3 and ERK1/2 eliminates radioresistant GBM cells
- Author
-
Xie, Bowen, Zhang, Lu, Hu, Wenfeng, Fan, Ming, Jiang, Nian, Duan, Yumei, Jing, Di, Xiao, Wenwu, Fragoso, Ruben C, Lam, Kit S, Sun, Lun-Quan, and Li, Jian Jian
- Subjects
Biochemistry and Cell Biology ,Medicinal and Biomolecular Chemistry ,Chemical Sciences ,Biological Sciences ,Orphan Drug ,Brain Cancer ,Radiation Oncology ,Cancer ,Brain Disorders ,Rare Diseases ,Neurosciences ,Animals ,Cell Line ,Tumor ,Disease Models ,Animal ,Enzyme Activation ,Gene Expression ,Genes ,Reporter ,Glioblastoma ,Humans ,Mice ,Mitogen-Activated Protein Kinase 1 ,Mitogen-Activated Protein Kinase 3 ,Mutation ,Prognosis ,Radiation Tolerance ,STAT3 Transcription Factor ,GBM ,Radiotherapy ,Radioresistance ,STAT3 ,ERK1/2 ,Tumor regrowth ,Medical Biochemistry and Metabolomics ,Pharmacology and Pharmaceutical Sciences ,Biochemistry and cell biology ,Medicinal and biomolecular chemistry - Abstract
Radiotherapy (RT) is the major modality for control of glioblastoma multiforme (GBM), the most aggressive brain tumor in adults with poor prognosis and low patient survival rate. To improve the RT efficacy on GBM, the mechanism causing tumor adaptive radioresistance which leads to the failure of tumor control and lethal progression needs to be further elucidated. Here, we conducted a comparative analysis of RT-treated recurrent tumors versus primary counterparts in GBM patients, RT-treated orthotopic GBM tumors xenografts versus untreated tumors and radioresistant GBM cells versus wild type cells. The results reveal that activation of STAT3, a well-defined redox-sensitive transcriptional factor, is causally linked with GBM adaptive radioresistance. Database analysis also agrees with the worse prognosis in GBM patients due to the STAT3 expression-associated low RT responsiveness. However, although the radioresistant GBM cells can be resensitized by inhibition of STAT3, a fraction of radioresistant cells can still survive the RT combined with STAT3 inhibition or CRISPR/Cas9-mediated STAT3 knockout. A complementally enhanced activation of ERK1/2 by STAT3 inhibition is identified responsible for the survival of the remaining resistant tumor cells. Dual inhibition of ERK1/2 and STAT3 remarkably eliminates resistant GBM cells and inhibits tumor regrowth. These findings demonstrate a previously unknown feature ofSTAT3-mediated ERK1/2 regulation and an effective combination of two targets in resensitizing GBM to RT.
- Published
- 2019
26. Combinatorial Peptide Microarray Synthesis Based on Microfluidic Impact Printing
- Author
-
Li, Jiannan, Zhao, Siwei, Yang, Gaomai, Liu, Ruiwu, Xiao, Wenwu, Disano, Paolo, Lam, Kit S, and Pan, Tingrui
- Subjects
Organic Chemistry ,Chemical Sciences ,Biotechnology ,Amines ,Combinatorial Chemistry Techniques ,Humans ,Integrin alpha4beta1 ,Jurkat Cells ,Microfluidic Analytical Techniques ,Peptide Library ,Peptides ,Printing ,Three-Dimensional ,Protein Array Analysis ,Surface Properties ,peptide synthesis ,microfluidic ,peptide microarrays ,printing ,cancer targeting ,integrin binding ,Biochemistry and cell biology ,Medicinal and biomolecular chemistry ,Organic chemistry - Abstract
In this Research Article, a novel inkjet printing technique, micro impact printing (MI printing), is applied for the first time to combinatorial peptide microarray synthesis on amine functionalized microdisc arrays through standard Fmoc chemistry. MI printing shows great advantages in combinatorial peptide microarray synthesis compared with other printing techniques, including (1) a disposable cartridge; (2) a small spot size (80 μm) increases array density; (3) minimal loading volume (0.6 μL) and dead volume (
- Published
- 2019
27. Novel window for cancer nanotheranostics: non-invasive ocular assessments of tumor growth and nanotherapeutic treatment efficacy in vivo.
- Author
-
Goswami, Mayank, Wang, Xinlei, Zhang, Pengfei, Xiao, Wenwu, Karlen, Sarah J, Li, Yuanpei, Zawadzki, Robert J, Burns, Marie E, Lam, Kit S, and Pugh, Edward N
- Subjects
Biomedical and Clinical Sciences ,Immunology ,Rare Diseases ,Nanotechnology ,Bioengineering ,Cancer ,Biotechnology ,Optical Physics ,Materials Engineering ,Ophthalmology and optometry ,Biomedical engineering ,Atomic ,molecular and optical physics - Abstract
In cancer research there is a fundamental need for animal models that allow the in vivo longitudinal visualization and quantification of tumor development, nanotherapeutic delivery, the tumor microenvironment including blood vessels, macrophages, fibroblasts, immune cells, and extracellular matrix, and the tissue response to treatment. To address this need, we developed a novel mouse ocular xenograft model. Green fluorescent protein (GFP) expressing human glioblastoma cells (between 500 and 10,000) were implanted into the subretinal space of immunodeficient mice (56 eyes). The resultant xenografts were imaged in vivo non-invasively with combined fluorescence scanning laser ophthalmoscopy (SLO) and volumetric optical coherence tomography (OCT) for a period up to several months. Most xenografts exhibited a latent phase followed by a stable or rapidly increasing volume, but about 1/3 underwent spontaneous remission. After prescribed growth, a population of tumors was treated with intravenously delivered doxorubicin-containing porphyrin and cholic acid-based nanoparticles ("nanodox"). Fluorescence resonance energy transfer (FRET) emission (doxorubicin → porphyrin) was used to localize nanodox in the xenografts, and 690 nm light exposure to activate it. Such photo-nanotherapy was highly effective in reducing tumor volume. Histopathology and flow cytometry revealed CD4 + and CD8 + immune cell infiltration of xenografts. Overall, the ocular model shows potential for examining the relationships between neoplastic growth, neovascularization and other features of the immune microenvironment, and for evaluating treatment response longitudinally in vivo.
- Published
- 2019
28. A polymer-free, biomimicry drug self-delivery system fabricated via a synergistic combination of bottom-up and top-down approaches
- Author
-
Xu, Xiaobao, Yang, Gaomai, Xue, Xiangdong, Lu, Hongwei, Wu, Hao, Huang, Yee, Jing, Di, Xiao, Wenwu, Tian, Jingkui, Yao, Wei, Pan, Chong-xian, Lin, Tzu-yin, and Li, Yuanpei
- Subjects
Chemical Engineering ,Engineering ,Biomedical Engineering ,Nanotechnology ,Bioengineering ,Cancer ,Generic health relevance ,Animals ,Antineoplastic Agents ,Cell Line ,Tumor ,Chlorophyll ,Drug Carriers ,Drug Liberation ,Erythrocyte Membrane ,Female ,Humans ,Irinotecan ,Light ,Mice ,Nude ,Nanoparticles ,Photochemotherapy ,Photosensitizing Agents ,Rats ,Sprague-Dawley ,Macromolecular and Materials Chemistry ,Macromolecular and materials chemistry ,Biomedical engineering ,Chemical engineering - Abstract
Compared to conventional carrier-assistant drug delivery systems (DDSs), drug self-delivery systems (DSDSs) have advantages of unprecedented drug loading capacity, minimized carrier-related toxicity and ease of preparation. However, the colloidal stability and blood circulation time of DSDSs still need to be improved. Here we report on the development of a novel biomimicry drug self-delivery system by the integration of a top-down cell membrane complexing technique into our self-delivery multifunctional nano-platform made from bottom-up approach that contains 100% active pharmaceutical ingredients (API) of Pheophorbide A and Irinotecan conjugates (named PI). Compared to conventional cell membrane coated nanoparticles with polymer framework as core and relatively low drug loading, this system consisting of red blood cell membrane vesicles complexed PI (RBC-PI) is polymer-free with up to 50% API loading. RBC-PI exhibited 10 times higher area under curve in pharmacokinetic study and much lower macrophage uptake compared with the parent PI nanoparticles. RBC-PI retained the excellent chemophototherapeutic effects of the PI nanoparticles, but possessed superior anti-cancer efficacy with prolonged blood circulation, improved tumor delivery, and enhanced photothermal effects in animal models. This system represents a novel example of using cell membrane complexing technique for effective surface modification of DSDSs. This is also an innovative study to form a polymer-free cell membrane nanoparticle complexing with positive surface charged materials. This biomimicry DSDS takes advantages of the best features from both systems to make up for each other's shortcomings and posed all the critical features for an ideal drug delivery system.
- Published
- 2018
29. A Plug-and-Play, Drug-on-Pillar Platform for Combination Drug Screening Implemented by Microfluidic Adaptive Printing
- Author
-
Li, Jiannan, Tan, Wen, Xiao, Wenwu, Carney, Randy P, Men, Yongfan, Li, Yuanpei, Quon, Gerald, Ajena, Yousif, Lam, Kit S, and Pan, Tingrui
- Subjects
Medicinal and Biomolecular Chemistry ,Chemical Sciences ,Cancer ,Breast Cancer ,Biotechnology ,Women's Health ,Bioengineering ,Antineoplastic Agents ,Cell Proliferation ,Cell Survival ,Dose-Response Relationship ,Drug ,Doxorubicin ,Drug Combinations ,Drug Evaluation ,Preclinical ,Drug Screening Assays ,Antitumor ,Humans ,Microfluidic Analytical Techniques ,Printing ,Three-Dimensional ,Structure-Activity Relationship ,Triple Negative Breast Neoplasms ,Tumor Cells ,Cultured ,Analytical Chemistry ,Other Chemical Sciences ,Medical biochemistry and metabolomics ,Analytical chemistry ,Chemical engineering - Abstract
Traditional high-throughput drug combination screening requires automatic pipetting of drugs into high-density microtiter plates. Here, a drug-on-pillar platform is proposed for efficient combination drug screening. Using the proposed approach, combination drug screening can be carried out in a plug-and-play manner, allowing for high-throughput screening of large permutations of drug combinations at various concentrations, such that drug dispensing and cell-based screening can be temporally separated and therefore can potentially be performed at distant laboratories. The dispensing is implemented using our recently developed microfluidic pneumatic printing platform, which features a low-cost disposable cartridge that minimizes cross contamination. Moreover, our previously developed drug nanoformulation method with amphiphilic telodendrimers has been utilized to maintain drug stability in a dry form, allowing for convenient drug storage, shipping, and subsequent rehydration. Combining the features described above, we have implemented a 1260-spot drug combination array to study the effect of paired drugs against MDA-MB-231 triple negative human breast cancer cells. This study supports the feasibility of the drug-on-pillar platform for combination drug screening and has provided valuable insight into drug combination efficacy against breast cancer.
- Published
- 2018
30. Effect of thickness scaling on the switching dynamics of ferroelectric HfO2–ZrO2 capacitors
- Author
-
Peng, Yue, Wang, Zhe, Xiao, Wenwu, Ma, Yu, Liu, Fenning, Deng, Xinran, Yu, Xiao, Liu, Yan, Han, Genquan, and Hao, Yue
- Published
- 2022
- Full Text
- View/download PDF
31. Synaptic Behaviors in Ferroelectric-Like Field-Effect Transistors with Ultrathin Amorphous HfO2 Film
- Author
-
Peng, Yue, Xiao, Wenwu, Zhang, Guoqing, Han, Genquan, Liu, Yan, and Hao, Yue
- Published
- 2022
- Full Text
- View/download PDF
32. SSA-over-array (SSoA): A stacked DRAM architecture for near-memory computing.
- Author
-
Jiang, Xiping, Bai, Fujun, Wang, Song, Guo, Yixin, Zuo, Fengguo, Xiao, Wenwu, Wang, Yubing, Yang, Jianguo, and Liu, Ming
- Published
- 2024
- Full Text
- View/download PDF
33. Effect of electrical stress on time dependent dielectric breakdown (TDDB) tolerate capability of HfO2–ZrO2 ferroelectric films with different thicknesses.
- Author
-
Peng, Yue, Wang, Zhe, Wu, Qiuxia, Zhang, Shuo, Ma, Wenxuan, Xiao, WenWu, Zhang, Chunfu, and Hao, Yue
- Subjects
DIELECTRIC breakdown ,TIME pressure ,FERROELECTRIC devices ,FERROELECTRIC materials ,RESEARCH personnel ,COMPLEMENTARY metal oxide semiconductors - Abstract
HfO
2 -based ferroelectric materials as the most promising candidate for the ferroelectric memories, have been widely studied for more than a decade due to their excellent ferroelectric properties and CMOS compatibility. In order to realize its industrialization as soon as possible, researchers have been devoted to improving the reliability performance, such as wake up, imprint, limited endurance, et al. Among them, the breakdown characteristic is one of main failure mechanisms of HfO2 -based ferroelectric devices, which limits the write/read reliability of the devices. Based on this, we systematically studied the effect of thickness on the time-dependent dielectric breakdown (TDDB) tolerate capability of HfO2 –ZrO2 (HZO) FE films under both forward and reverse electrical stress conditions. The thickness of HZO FE film ranged from 6 to 20 nm. Our findings reveal that decreasing the thickness of the HZO FE film leads to an improvement in TDDB tolerance capability which is attributed to the fact that higher density of oxygen vacancies in thinner HZO FE films can effectively inhibit the generation of new oxygen vacancies and the growth of conductive filaments, thus effectively improving the TDDB characteristics. These results provide a potential solution for mitigating breakdown characteristics of HfO2 -based ferroelectric devices in memory applications. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
34. Targeting Galectin-1 Impairs Castration-Resistant Prostate Cancer Progression and Invasion
- Author
-
Shih, Tsung-Chieh, Liu, Ruiwu, Wu, Chun-Te, Li, Xiaocen, Xiao, Wenwu, Deng, Xiaojun, Kiss, Sophie, Wang, Ting, Chen, Xiao-Jia, Carney, Randy, Kung, Hsing-Jien, Duan, Yong, Ghosh, Paramita M, and Lam, Kit S
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Biotechnology ,Prostate Cancer ,Cancer ,Urologic Diseases ,5.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,Androgen Antagonists ,Animals ,Cell Line ,Tumor ,Cell Movement ,Cell Proliferation ,Disease Progression ,Galectin 1 ,Gene Expression Regulation ,Neoplastic ,Humans ,Male ,Mice ,Neoplasm Invasiveness ,Neoplasm Metastasis ,Prostatic Neoplasms ,Castration-Resistant ,Receptors ,Androgen ,Tissue Array Analysis ,Xenograft Model Antitumor Assays ,Oncology & Carcinogenesis ,Clinical sciences ,Oncology and carcinogenesis - Abstract
Purpose: The majority of patients with prostate cancer who are treated with androgen-deprivation therapy (ADT) will eventually develop fatal metastatic castration-resistant prostate cancer (mCRPC). Currently, there are no effective durable therapies for patients with mCRPC. High expression of galectin-1 (Gal-1) is associated with prostate cancer progression and poor clinical outcome. The role of Gal-1 in tumor progression is largely unknown. Here, we characterized Gal-1 functions and evaluated the therapeutic effects of a newly developed Gal-1 inhibitor, LLS30, in mCRPC.Experimental Design: Cell viability, colony formation, migration, and invasion assays were performed to examine the effects of inhibition of Gal-1 in CRPC cells. We used two human CRPC xenograft models to assess growth-inhibitory effects of LLS30. Genome-wide gene expression analysis was conducted to elucidate the effects of LLS30 on metastatic PC3 cells.Results: Gal-1 was highly expressed in CRPC cells, but not in androgen-sensitive cells. Gal-1 knockdown significantly inhibited CRPC cells' growth, anchorage-independent growth, migration, and invasion through the suppression of androgen receptor (AR) and Akt signaling. LLS30 targets Gal-1 as an allosteric inhibitor and decreases Gal-1-binding affinity to its binding partners. LLS30 showed in vivo efficacy in both AR-positive and AR-negative xenograft models. LLS30 not only can potentiate the antitumor effect of docetaxel to cause complete regression of tumors, but can also effectively inhibit the invasion and metastasis of prostate cancer cells in vivoConclusions: Our study provides evidence that Gal-1 is an important target for mCRPC therapy, and LLS30 is a promising small-molecule compound that can potentially overcome mCRPC. Clin Cancer Res; 24(17); 4319-31. ©2018 AACR.
- Published
- 2018
35. Simvastatin Overcomes Resistance to Tyrosine Kinase Inhibitors in Patient-derived, Oncogene-driven Lung Adenocarcinoma Models
- Author
-
Ma, Weijie, primary, Wei, Sixi, additional, Li, Qianping, additional, Zeng, Jie, additional, Xiao, Wenwu, additional, Zhou, Chihong, additional, Yoneda, Ken Y., additional, Zeki, Amir A., additional, and Li, Tianhong, additional
- Published
- 2024
- Full Text
- View/download PDF
36. Transformable amyloid-beta mimetic peptide amphiphiles for lysosomal disruption in non-small cell lung cancer
- Author
-
Baehr, Christopher M., Zhang, Lu, Wu, Yi, Domokos, Andras, Xiao, Wenwu, Wang, Lei, and Lam, Kit S.
- Published
- 2021
- Full Text
- View/download PDF
37. Extremely long tumor retention, multi-responsive boronate crosslinked micelles with superior therapeutic efficacy for ovarian cancer
- Author
-
Xiao, Wenwu, Suby, Nell, Xiao, Kai, Lin, Tzu-yin, Al Awwad, Nasir, Lam, Kit S, and Li, Yuanpei
- Subjects
Medical Biotechnology ,Biomedical and Clinical Sciences ,Biotechnology ,Bioengineering ,Cancer ,Nanotechnology ,Orphan Drug ,Ovarian Cancer ,Rare Diseases ,Women's Health ,5.1 Pharmaceuticals ,Animals ,Antineoplastic Agents ,Phytogenic ,Boronic Acids ,Catechols ,Cell Line ,Tumor ,Drug Delivery Systems ,Female ,Mice ,Micelles ,Nanoparticles ,Ovarian Neoplasms ,Paclitaxel ,Tumor Burden ,Long-term tumor retention ,Boronate crosslinked micelles ,Multi-responsive ,FRET ,Ovarian cancer ,Biomedical Engineering ,Chemical Engineering ,Pharmacology and Pharmaceutical Sciences ,Pharmacology & Pharmacy ,Pharmacology and pharmaceutical sciences ,Biomedical engineering - Abstract
Mortality rates for ovarian cancer have declined only slightly in the past forty years since the "War on Cancer" was declared. The current standard care of ovarian cancer is still cytoredutive surgery followed by several cycles of chemotherapy. The severe adverse effect from chemotherapy drug is a leading cause for the patients to fail in long term therapy post-surgery. New nanocarriers able to minimize the premature drug release in blood circulation while releasing drug on-demand at tumor site have profound impact on the improvement of the efficacy and toxicity profile of the chemotherapeutic drugs. Here we reported a unique type of extremely long tumor retention, multi-responsive boronate crosslinked micelles (BCM) for ovarian cancer therapy. We systemically investigated the stability of BCM in serum and plasma, and their responsiveness to acidic pH and cis-diols (such as mannitol, a safe FDA approved drug for diuresis) through particle size measurement and förster resonance energy transfer (FRET) approach. Paclitaxel (PTX) loaded BCM (BCM-PTX) exhibited higher stability than non-crosslinked micelles (NCM) in the presence of plasma or serum. BCMs possessed a longer in vivo blood circulation time when compared to NCM. Furthermore, BCM could be disassembled in an acidic pH environment or by administrating mannitol, facilitating drug release in an acidic tumor environment and triggered by exogenous stimuli after drug enrichment in tumor mass. Near infra-red fluorescence (NIRF) imaging on SKOV-3 ovarian cancer mouse model demonstrated that the NIR dye DiD encapsulated BCM could preferentially accumulate in tumor site and their tumor retention was very long with still 66% remained on 12th day post injection. DiD-NCM had similar high-level uptake in tumor with DiD-BCM within the first 3days, its accumulation, however, decreased obviously on 4th day and only 15% dye was left 12days later. In both formulations, the dye uptake in normal organs was mostly washed away within the first 24-48h. In in vivo tumor treatment study, PTX loaded BCM showed superior therapeutic efficacy than that of NCM and Taxol. The mice could tolerate 20mg/kg PTX formulated in nano-formulations, which doubled the maximum tolerated dose (MTD) of Taxol. The administration of mannitol 24h after BCM-PTX injection further improved the tumor therapeutic effect and elongated the survival time of the mice. The novel boronate-catechol crosslinked nanocarrier platform demonstrated its superior capability in targeted drug delivery, which is not only useful for ovarian cancer treatment but will also be beneficial for the therapy of many other solid tumors.
- Published
- 2017
38. Cholic acid-based novel micellar nanoplatform for delivering FDA-approved taxanes
- Author
-
Bharadwaj, Gaurav, Nhan, Viet, Yang, ShanChao, Li, Xiaocen, Narayanan, Anand, Macarenco, Ana Carolina, Shi, Yu, Yang, Darrion, Vieira, Letcia Salvador, Xiao, Wenwu, Li, Yuanpei, and Lam, Kit S
- Subjects
Medical Biotechnology ,Biomedical and Clinical Sciences ,Antineoplastic Agents ,Bridged-Ring Compounds ,Cell Line ,Tumor ,Cholic Acid ,Docetaxel ,Drug Carriers ,Humans ,Micelles ,Nanoparticles ,Neoplasms ,Paclitaxel ,Taxoids ,cabazitaxel ,cholic acid ,docetaxel ,drug delivery ,micelle ,nanoparticle ,paclitaxel ,taxane ,telodendrimer ,Physical Chemistry (incl. Structural) ,Nanotechnology ,Nanoscience & Nanotechnology ,Medical biotechnology ,Biomedical engineering - Abstract
AimTo structurally modify our existing cholic acid (CA)-based telodendrimer (TD; PEG5K-CA8) for effective micellar nanoencapsulation and delivery of the US FDA-approved members of taxane family.Materials & methodsGeneration of hybrid TDs was achieved by replacing four of the eight CAs with biocompatible organic moieties using solution-phase peptide synthesis. Drug loading was done using the standard evaporation method.ResultsHybrid TDs can generate micelles with narrow size distributions, low critical micelle concentration values (1-6 μM), better hematocompatibility and lack of in vitro cytotoxicity.ConclusionAlong with PEG5K-CA8, CA-based hybrid nanoplatform is the first of its kind that can stably encapsulate all three FDA-approved taxanes with nearly 100% efficiency up to 20% (w/w) loading.
- Published
- 2017
39. Discovery and Characterization of a Potent and Specific Peptide Ligand Targeting Endothelial Progenitor Cells and Endothelial Cells for Tissue Regeneration
- Author
-
Hao, Dake, Xiao, Wenwu, Liu, Ruiwu, Kumar, Priyadarsini, Li, Yuanpei, Zhou, Ping, Guo, Fuzheng, Farmer, Diana L, Lam, Kit S, Wang, Fengshan, and Wang, Aijun
- Subjects
Biochemistry and Cell Biology ,Biological Sciences ,Regenerative Medicine ,Stem Cell Research ,Stem Cell Research - Nonembryonic - Non-Human ,Binding Sites ,Cell Adhesion ,Cells ,Cultured ,Drug Discovery ,Endothelial Cells ,Endothelial Progenitor Cells ,Humans ,Integrins ,Ligands ,Peptides ,Regeneration ,Tissue Scaffolds ,Chemical Sciences ,Organic Chemistry ,Biological sciences ,Chemical sciences - Abstract
Endothelial progenitor cells (EPCs) and endothelial cells (ECs) play a vital role in endothelialization and vascularization for tissue regeneration. Various EPC/EC targeting biomolecules have been investigated to improve tissue regeneration with limited success often due to their limited functional specificity and structural stability. One-bead one-compound (OBOC) combinatorial technology is an ultrahigh throughput chemical library synthesis and screening method suitable for ligand discovery against a wide range of biological targets, such as integrins. In this study, using primary human EPCs/ECs as living probes, we identified an αvβ3 integrin ligand LXW7 discovered by OBOC combinatorial technology as a potent and specific EPC/EC targeting ligand. LXW7 overcomes the major barriers of other functional biomolecules that have previously been used to improve vascularization for tissue regeneration and possesses optimal stability, EPC/EC specificity, and functionality. LXW7 is a disulfide cyclic octa-peptide (cGRGDdvc) containing unnatural amino acids flanking both sides of the main functional motif; therefore it will be more resistant to proteolysis and more stable in vivo compared to linear peptides and peptides consisting of only natural amino acids. Compared with the conventional αvβ3 integrin ligand GRGD peptide, LXW7 showed stronger binding affinity to primary EPCs/ECs but weaker binding to platelets and no binding to THP-1 monocytes. In addition, ECs bound to the LXW7 treated culture surface exhibited enhanced biological functions such as proliferation, likely due to increased phosphorylation of VEGF receptor 2 (VEGF-R2) and activation of mitogen-activated protein kinase (MAPK) ERK1/2. Surface modification of electrospun microfibrous PLLA/PCL biomaterial scaffolds with LXW7 via Click chemistry resulted in significantly improved endothelial coverage. LXW7 and its derivatives hold great promise for EPC/EC recruitment and delivery and can be widely applied to functionalize various biological and medical materials to improve endothelialization and vascularization for tissue regeneration applications.
- Published
- 2017
40. Tumor-targeting peptides from combinatorial libraries
- Author
-
Liu, Ruiwu, Li, Xiaocen, Xiao, Wenwu, and Lam, Kit S
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Biomedical Imaging ,Cancer ,5.1 Pharmaceuticals ,Animals ,Combinatorial Chemistry Techniques ,Humans ,Ligands ,Neoplasms ,Peptide Library ,Peptides ,Protein Binding ,Tumor-targeting peptide ,Biological library ,Phage-display peptide library ,One-bead one-compound peptide library ,High throughput screening ,Cell surface receptor ,Pharmacology and Pharmaceutical Sciences ,Pharmacology & Pharmacy ,Pharmacology and pharmaceutical sciences - Abstract
Cancer is one of the major and leading causes of death worldwide. Two of the greatest challenges in fighting cancer are early detection and effective treatments with no or minimum side effects. Widespread use of targeted therapies and molecular imaging in clinics requires high affinity, tumor-specific agents as effective targeting vehicles to deliver therapeutics and imaging probes to the primary or metastatic tumor sites. Combinatorial libraries such as phage-display and one-bead one-compound (OBOC) peptide libraries are powerful approaches in discovering tumor-targeting peptides. This review gives an overview of different combinatorial library technologies that have been used for the discovery of tumor-targeting peptides. Examples of tumor-targeting peptides identified from each combinatorial library method will be discussed. Published tumor-targeting peptide ligands and their applications will also be summarized by the combinatorial library methods and their corresponding binding receptors.
- Published
- 2017
41. Discovery and characterization of a high-affinity and high-specificity peptide ligand LXY30 for in vivo targeting of α3 integrin-expressing human tumors
- Author
-
Xiao, Wenwu, Li, Tianhong, Bononi, Fernanda C, Lac, Diana, Kekessie, Ivy A, Liu, Yanlei, Sanchez, Eduardo, Mazloom, Anisha, Ma, Ai-hong, Lin, Jia, Tran, Jimmy, Yang, Kevin, Lam, Kit S, and Liu, Ruiwu
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Brain Cancer ,Brain Disorders ,Rare Diseases ,Biomedical Imaging ,Development of treatments and therapeutic interventions ,5.1 Pharmaceuticals ,Cancer-targeting peptide ,alpha 3 beta 1 integrin ,One-bead one-compound combinatorial peptide library ,Glioblastoma ,Optical imaging ,α3β1 integrin ,Medical Biochemistry and Metabolomics ,Clinical Sciences ,Clinical sciences ,Oncology and carcinogenesis - Abstract
Backgroundα3β1 integrin is overexpressed in several types of human cancer and is associated with poor prognosis, metastasis, and resistance to cancer treatment. We previously identified a cyclic peptide ligand LXY1 that specifically binds to the α3β1 integrin on human glioblastoma U-87MG cells. Here, we optimized LXY1 through one-bead one-compound combinatorial library screening and site-specific modifications to improve its in vivo binding property.MethodsThree bead libraries were synthesized and whole-cell binding assays were performed. The binding capacity of individual peptide ligands against different tumor cells was determined by flow cytometry and confirmed by optical imaging. A complex joining biotinylated ligand with streptavidin-Cy5.5 was used for in vivo target imaging in both subcutaneous and orthotopic U-87MG xenograft mouse models.ResultsLXY30, a cyclic peptide with the sequence cdG-Phe(3,5-diF)-G-Hyp-NcR, emerged as the most potent and selective ligand for the α3 subunit of α3β1 integrin with improved in vitro and in vivo tumor-targeting effects compared to LXY1 in U-87MG cells. LXY30 is considerably stable in plasma as demonstrated in an in vitro stability study in 90 % human plasma. LXY30 also binds to several other known α3β1 integrin-expressing glioblastoma, lung, and breast cancer cell lines with various affinities.ConclusionsOur data support further investigating the role of LXY30 as a human tumor-targeting peptide ligand for systemic and intracranial delivery of imaging agents and cancer therapeutics.
- Published
- 2016
42. HfO2–ZrO2 Ferroelectric Capacitors with Superlattice Structure: Improving Fatigue Stability, Fatigue Recovery, and Switching Speed
- Author
-
Kang, Mingshuang, primary, Peng, Yue, additional, Xiao, Wenwu, additional, Zhang, Yueyuan, additional, Wang, Zhe, additional, Du, Peiyuan, additional, Jiang, Hao, additional, Liu, Fenning, additional, Liu, Yan, additional, Hao, Yue, additional, and Han, Genquan, additional
- Published
- 2024
- Full Text
- View/download PDF
43. Developing a Nanoparticle-Delivered High-Efficacy Treatment for Infantile Hemangiomas Using a Mouse Hemangioendothelioma Model.
- Author
-
Orbay, Hakan, Li, Yuanpei, Xiao, Wenwu, Cherry, Simon R, Lam, Kit, and Sahar, David E
- Subjects
Animals ,Mice ,Mice ,Nude ,Hemangioendothelioma ,Skin Neoplasms ,Neoplasms ,Experimental ,Porphyrins ,Photosensitizing Agents ,Positron-Emission Tomography ,Treatment Outcome ,Photochemotherapy ,Injections ,Intravenous ,Female ,Nanoparticles ,Nude ,Neoplasms ,Experimental ,Injections ,Intravenous ,Surgery ,Clinical Sciences - Abstract
BackgroundCurrent treatments for infantile hemangiomas have unpredictable outcomes. The authors' aim was to develop a nanoporphyrin-delivered, high-efficacy treatment for infantile hemangiomas using a mouse hemangioendothelioma model.MethodsThe authors injected mouse hemangioendothelioma cells intradermally to axillary regions of 5-week-old, female, nude mice (n = 19) to induce hemangioendothelioma growth. They documented nanoporphyrin accumulation in hemangioendotheliomas using positron emission tomography. For the treatment study, the authors randomized hemangioendothelioma-bearing nude mice (n = 9) into three groups (n = 3 each). Group I received only saline injections. Group II received only laser treatment after saline injection, and group III received laser treatment after nanoporphyrin injection through the tail vein. The authors followed up the treatment response with digital caliper measurements.ResultsHemangioendotheliomas started to grow approximately 1 week after inoculation and resembled infantile hemangiomas histologically. Nanoporphyrin uptake in hemangioendotheliomas was 19.7 ± 2.2, 16.7 ± 2.02, 8.4 ± 0.3, and 4.9 ± 0.6 percent injected dose per gram of tissue at 3, 6, 24, and 48 hours after injection, respectively. Nanoporphyrin uptake was significantly higher than in blood at 24 and 48 hours after injection (p < 0.05). Results of ex vivo biodistribution study were consistent with positron emission tomographic imaging. Hemangioendotheliomas in group III started to regress 1 day after the treatment and disappeared totally by day 21. The difference between tumor volumes in group III and other groups was significant on days 17 and 21 (p < 0.05).ConclusionsNanoporphyrin accumulated in hemangioendotheliomas at high concentrations, enabling a high-efficacy photodynamic therapy. Given the similarities between hemangioendotheliomas and infantile hemangiomas, this treatment potentially can be a high-efficacy treatment for infantile hemangiomas.
- Published
- 2016
44. Optimization of RGD-Containing Cyclic Peptides against αvβ3 Integrin
- Author
-
Wang, Yan, Xiao, Wenwu, Zhang, Yonghong, Meza, Leah, Tseng, Harry, Takada, Yoshikazu, Ames, James B, and Lam, Kit S
- Subjects
Biochemistry and Cell Biology ,Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Biological Sciences ,Rare Diseases ,Cancer ,Biotechnology ,5.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,Animals ,Cell Line ,Tumor ,Combinatorial Chemistry Techniques ,Drug Delivery Systems ,Glioblastoma ,Humans ,Integrin alphaVbeta3 ,K562 Cells ,Mice ,Mice ,Nude ,Molecular Structure ,Peptides ,Cyclic ,Structure-Activity Relationship ,Pharmacology and Pharmaceutical Sciences ,Oncology & Carcinogenesis ,Biochemistry and cell biology ,Oncology and carcinogenesis - Abstract
We have previously reported the use of one-bead-one-compound (OBOC) combinatorial technology to develop a disulfide cyclic, Arg-Gly-Asp-containing octapeptide LXW7 (cGRGDdvc), that targets αvβ3 integrin with high affinity and specificity. αvβ3 integrin is known to be overexpressed in many cancers and in tumor vasculature, and it has been established as a cancer therapeutic target. To further optimize LXW7, we have performed systematic structure-activity relationship studies. On the basis of the results, two highly focused OBOC peptide libraries were designed, synthesized, and screened against αvβ3 integrin-transfected K562 cells. One of the best ligands, LXW64, was found to have 6.6-fold higher binding affinity than LXW7, and showed preferential binding to cells expressing αvβ3 integrin. In addition to binding strongly to U-87MG glioblastoma cells in vitro, LXW64 also targets U-87MG xenografts implanted in nude mice, indicating that it is an excellent vehicle for the delivery of cytotoxic payload to tumors and tumor blood vessels that overexpress αvβ3 integrin. Mol Cancer Ther; 15(2); 232-40. ©2015 AACR.
- Published
- 2016
45. Band alignments at Hf1-xZrxO2/Si and Hf0.52Zr0.48O2/Si0.55Ge0.45 interfaces
- Author
-
Peng, Yue, Han, Genquan, Xiao, Wenwu, Liu, Yan, Li, Qinglong, Zhang, Chunfu, Zhang, Jincheng, and Hao, Yue
- Published
- 2019
- Full Text
- View/download PDF
46. Nanomicelle formulation modifies the pharmacokinetic profiles and cardiac toxicity of daunorubicin
- Author
-
Zhang, Hongyong, Li, Yuanpei, Lin, Tzu-yin, Xiao, Kai, Haddad, Ashraf S, Henderson, Paul T, Jonas, Brian A, Chen, Mingyi, Xiao, Wenwu, Liu, Ruiwu, Lam, Kit S, and Pan, Chong-xian
- Subjects
Medical Biotechnology ,Biomedical and Clinical Sciences ,Heart Disease ,Cardiovascular ,Hematology ,Cancer ,Animals ,Antibiotics ,Antineoplastic ,Cardiotoxicity ,Caspases ,Chemistry ,Pharmaceutical ,Daunorubicin ,Dendrimers ,Drug Delivery Systems ,Leukemia ,Myeloid ,Acute ,Male ,Mice ,Mice ,Inbred BALB C ,Micelles ,Myocardium ,Nanomedicine ,Neoplastic Stem Cells ,Rats ,Rats ,Sprague-Dawley ,cardiotoxicity ,daunorubicin ,leukemia stem cells ,nanomicelles ,pharmacokinetics ,Physical Chemistry (incl. Structural) ,Nanotechnology ,Nanoscience & Nanotechnology ,Medical biotechnology ,Biomedical engineering - Abstract
BackgroundTreatment with daunorubicin (DNR) in acute myeloid leukemia is moderately effective and associated with significant side effects, including cardiac toxicity. We recently developed a nanomicellar formulation of DNR that specifically targets acute myeloid leukemia stem cells.Materials & methodsPharmacokinetics analysis of free DNR, DNR in nanomicellar formulations was performed in Balb/c mice and Sprague-Dawley rats. Histochemical staining, caspase 3/7, troponin and creatine kinase MB isoenzyme were used to assess toxicity.ResultsCompared with free DNR, the nanomicellar formulations of DNR had less cardiotoxicity as evidenced by milder histopathological changes, lower caspase 3/7 activity in heart tissue (p = 0.002), lower plasma creatine kinase MB isoenzyme (p = 0.002) and troponin concentrations (p = 0.001) postinjection. The area under curve concentration of DNR in micelles increased by 31.9-fold in mice (p < 0.0001) and 22.0-fold higher in rats (p < 0.001).ConclusionLeukemia stem cell-targeting micelles dramatically change the pharmacokinetics and reduce the cardiac toxicity of DNR, which may enable improved DNR-based treatment of acute myeloid leukemia.
- Published
- 2014
47. Mechanochemotransduction During Cardiomyocyte Contraction Is Mediated by Localized Nitric Oxide Signaling
- Author
-
Jian, Zhong, Han, Huilan, Zhang, Tieqiao, Puglisi, Jose, Izu, Leighton T, Shaw, John A, Onofiok, Ekama, Erickson, Jeffery R, Chen, Yi-Je, Horvath, Balazs, Shimkunas, Rafael, Xiao, Wenwu, Li, Yuanpei, Pan, Tingrui, Chan, James, Banyasz, Tamas, Tardiff, Jil C, Chiamvimonvat, Nipavan, Bers, Donald M, Lam, Kit S, and Chen-Izu, Ye
- Subjects
Biochemistry and Cell Biology ,Biological Sciences ,Cardiovascular ,Pediatric ,Bioengineering ,Rare Diseases ,Heart Disease ,Aetiology ,Development of treatments and therapeutic interventions ,2.1 Biological and endogenous factors ,5.1 Pharmaceuticals ,Animals ,Calcium-Calmodulin-Dependent Protein Kinase Type 2 ,Diastole ,Heart ,Mechanotransduction ,Cellular ,Mice ,Mice ,Inbred C57BL ,Mice ,Transgenic ,Myocytes ,Cardiac ,Nitric Oxide ,Nitric Oxide Synthase ,Signal Transduction ,Systole ,Biochemistry and cell biology - Abstract
Cardiomyocytes contract against a mechanical load during each heartbeat, and excessive mechanical stress leads to heart diseases. Using a cell-in-gel system that imposes an afterload during cardiomyocyte contraction, we found that nitric oxide synthase (NOS) was involved in transducing mechanical load to alter Ca(2+) dynamics. In mouse ventricular myocytes, afterload increased the systolic Ca(2+) transient, which enhanced contractility to counter mechanical load but also caused spontaneous Ca(2+) sparks during diastole that could be arrhythmogenic. The increases in the Ca(2+) transient and sparks were attributable to increased ryanodine receptor (RyR) sensitivity because the amount of Ca2(+) in the sarcoplasmic reticulum load was unchanged. Either pharmacological inhibition or genetic deletion of nNOS (or NOS1), but not of eNOS (or NOS3), prevented afterload-induced Ca2(+) sparks. This differential effect may arise from localized NO signaling, arising from the proximity of nNOS to RyR, as determined by super-resolution imaging. Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) and nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) also contributed to afterload-induced Ca(2+) sparks. Cardiomyocytes from a mouse model of familial hypertrophic cardiomyopathy exhibited enhanced mechanotransduction and frequent arrhythmogenic Ca(2+) sparks. Inhibiting nNOS and CaMKII, but not NOX2, in cardiomyocytes from this model eliminated the Ca2(+) sparks, suggesting mechanotransduction activated nNOS and CaMKII independently from NOX2. Thus, our data identify nNOS, CaMKII, and NOX2 as key mediators in mechanochemotransduction during cardiac contraction, which provides new therapeutic targets for treating mechanical stress-induced Ca(2+) dysregulation, arrhythmias, and cardiomyopathy.
- Published
- 2014
48. A smart and versatile theranostic nanomedicine platform based on nanoporphyrin
- Author
-
Li, Yuanpei, Lin, Tzu-yin, Luo, Yan, Liu, Qiangqiang, Xiao, Wenwu, Guo, Wenchang, Lac, Diana, Zhang, Hongyong, Feng, Caihong, Wachsmann-Hogiu, Sebastian, Walton, Jeffrey H, Cherry, Simon R, Rowland, Douglas J, Kukis, David, Pan, Chongxian, and Lam, Kit S
- Subjects
Medical Biotechnology ,Biomedical and Clinical Sciences ,Bioengineering ,Biomedical Imaging ,Nanotechnology ,5.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,Cancer ,Animals ,Cell Line ,Tumor ,Dendrimers ,Doxorubicin ,Drug Carriers ,Female ,Fluorescence ,Humans ,Magnetic Resonance Imaging ,Male ,Mice ,Nude ,Mice ,Transgenic ,Nanostructures ,Photochemotherapy ,Porphyrins ,Rats ,Sprague-Dawley ,Reactive Oxygen Species ,Spectroscopy ,Near-Infrared ,Theranostic Nanomedicine - Abstract
Multifunctional nanoparticles with combined diagnostic and therapeutic functions show great promise towards personalized nanomedicine. However, attaining consistently high performance of these functions in vivo in one single nanoconstruct remains extremely challenging. Here we demonstrate the use of one single polymer to develop a smart 'all-in-one' nanoporphyrin platform that conveniently integrates a broad range of clinically relevant functions. Nanoporphyrins can be used as amplifiable multimodality nanoprobes for near-infrared fluorescence imaging (NIRFI), magnetic resonance imaging (MRI), positron emission tomography (PET) and dual modal PET-MRI. Nanoporphyrins greatly increase the imaging sensitivity for tumour detection through background suppression in blood, as well as preferential accumulation and signal amplification in tumours. Nanoporphyrins also function as multiphase nanotransducers that can efficiently convert light to heat inside tumours for photothermal therapy (PTT), and light to singlet oxygen for photodynamic therapy (PDT). Furthermore, nanoporphyrins act as programmable releasing nanocarriers for targeted delivery of drugs or therapeutic radio-metals into tumours.
- Published
- 2014
49. Discovery of Specific Ligands for Oral Squamous Carcinoma to Develop Anti-cancer Drug Loaded Precise Targeting Nanotherapeutics
- Author
-
Yang, Fan, Liu, Ruiwu, Kramer, Randall, Xiao, Wenwu, Jordan, Richard, and Lam, Kit S
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Biotechnology ,Orphan Drug ,Cancer ,Digestive Diseases ,Dental/Oral and Craniofacial Disease ,Rare Diseases ,Development of treatments and therapeutic interventions ,5.9 Resources and infrastructure (treatment development) ,5.1 Pharmaceuticals ,Antineoplastic Agents ,Carcinoma ,Squamous Cell ,Cell Line ,Cell Line ,Tumor ,Coloring Agents ,Combinatorial Chemistry Techniques ,Drug Design ,Endothelial Cells ,Erythrocytes ,Fibroblasts ,Hemolysis ,High-Throughput Screening Assays ,Humans ,Keratinocytes ,Leukocytes ,Ligands ,Molecular Targeted Therapy ,Mouth Neoplasms ,Nanomedicine ,Neoplasm Proteins ,Protein Binding ,Dentistry - Abstract
Oral squamous cell carcinoma has a low five-year survival rate, which may be due to late detection and a lack of effective tumor-specific therapies. Using a high throughput drug discovery strategy termed one-bead one-compound combinatorial library, the authors identified six compounds with high binding affinity to different human oral squamous cell carcinoma cell lines but not to normal cells. Current work is under way to develop these ligands to oral squamous cell carcinoma specific imaging probes or therapeutic agents.
- Published
- 2012
50. HfO2–ZrO2 Superlattice Ferroelectric Field-Effect Transistor With Improved Endurance and Fatigue Recovery Performance
- Author
-
Peng, Yue, primary, Xiao, Wenwu, additional, Liu, Fenning, additional, Jin, Chengji, additional, Cheng, Yan, additional, Wang, Luhua, additional, Zhang, Yueyuan, additional, Yu, Xiao, additional, Liu, Yan, additional, Hao, Yue, additional, and Han, Genquan, additional
- Published
- 2023
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.