MOLECULAR PHARMACEUTICS
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2021
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IF 4.939
Zhiting Sun,Xiaoxiao Wang,Jing Liu,Zhihong Wang,Weiwei Wang,Deling Kong,Xigang Leng
Photodynamic therapy (PDT) is promising for clinical cancer therapy; however, the efficacy was limited as an individual treatment regimen. Here, an approach synergistically combining PDT and nitric oxide (NO) gas therapy along with destruction of the tumor extracellular matrix (ECM) was presented to eliminate cancer. Specifically, the NO donor l-arginine (l-Arg) and the photosensitizer indocyanine green (ICG) were co-encapsulated in poly(lactic-glycolic acid) (PLGA) nanoparticles and then loaded into the poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL–PEG–PCL) hydrogel to develop an injectable, thermosensitive dual drug delivery system (PLGA@ICG@l-Arg/Gel). Significantly, reactive oxygen species (ROS) produced by PLGA@ICG@l-Arg/Gel under near-infrared (NIR) light irradiation could not only result in the apoptosis of cancer cells but also oxidize l-Arg to generate NO, which could suppress the proliferation of cancer cells. Moreover, ROS could further oxidize NO to generate peroxynitrite anions (ONOO–). ONOO– could activate matrix metalloproteinases (MMPs), which notably degraded collagen in ECM so as to damage the tumor microenvironment. PLGA@ICG@l-Arg/Gel significantly increased the antitumor efficacy against highly malignant 4T1 tumors in mice. Taken together, PLGA@ICG@l-Arg/Gel is a multifunctional platform that provides a novel strategy for cancer treatment with cascade amplification of the ROS oxidation effect, which holds great potential in clinical translation.
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高影响因子
Oncotarget
·
2017
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IF 5.168
Na Huang,Shuai Lu,Xiao-Ge Liu,Jie Zhu,Yu-Jiong Wang,Rui-Tian Liu
Alzheimer's disease (AD) is the most common form of dementia, characterized by the formation of extracellular senile plaques and neuronal loss caused by amyloid β (Aβ) aggregates in the brains of AD patients. Conventional strategies failed to treat AD in clinical trials, partly due to the poor solubility, low bioavailability and ineffectiveness of the tested drugs to cross the blood-brain barrier (BBB). Moreover, AD is a complex, multifactorial neurodegenerative disease; one-target strategies may be insufficient to prevent the processes of AD. Here, we designed novel kind of poly(lactide-co-glycolic acid) (PLGA) nanoparticles by loading with Aβ generation inhibitor S1 (PQVGHL peptide) and curcumin to target the detrimental factors in AD development and by conjugating with brain targeting peptide CRT (cyclic CRTIGPSVC peptide), an iron-mimic peptide that targets transferrin receptor (TfR), to improve BBB penetration. The average particle size of drug-loaded PLGA nanoparticles and CRT-conjugated PLGA nanoparticles were 128.6 nm and 139.8 nm, respectively. The results of Y-maze and new object recognition test demonstrated that our PLGA nanoparticles significantly improved the spatial memory and recognition in transgenic AD mice. Moreover, PLGA nanoparticles remarkably decreased the level of Aβ, reactive oxygen species (ROS), TNF-α and IL-6, and enhanced the activities of super oxide dismutase (SOD) and synapse numbers in the AD mouse brains. Compared with other PLGA nanoparticles, CRT peptide modified-PLGA nanoparticles co-delivering S1 and curcumin exhibited most beneficial effect on the treatment of AD mice, suggesting that conjugated CRT peptide, and encapsulated S1 and curcumin exerted their corresponding functions for the treatment.
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高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Jingtao Du,Daniel Rybak,Qi Su,Qiusheng Wang,Qifan Yuan,Jinlong Gao,Yuhang Wang,Paweł Nakielski,Xianfeng Wang,Filippo Pierini,Jianyong Yu,Xiaoran Li,Bin Ding
The treatment of infected irregular wounds remains one of the most significant challenges in clinical practice. Sprayable hydrogels have attracted considerable attention due to their favorable fitting with irregular wounds. However, the development of hydrogels with programmable anti-bacterial, anti-inflammatory, and regenerative properties to match the healing process still faces severe challenges. Herein, a versatile strategy is demonstrated to develop sprayable and photothermal fiber-embedded hydrogel dressings by incorporating the gold nanorods (AuNRs) and anti-inflammatory drug diclofenac sodium (DS)-loaded poly(lactic- co -glycolic acid) (PLGA) electrospun fibers into the stromal-cell-derived factor 1α (SDF-1α)-immobilized gelatin methacrylate hydrogel. Benefiting from the photothermal conversion property of AuNRs and the suitable glass transition temperature of PLGA short fibers, the hydrogels can not only realize a photothermal anti-bacterial effect, but also photo-triggered on-demand release of DS for anti-inflammatory activity. Furthermore, the sustained release of SDF-1α facilitates endogenous stem cell recruitment. The in vivo experiments demonstrate accelerated healing of infected wounds. The RNA-sequencing analysis reveals that the hydrogel is capable of suppressing the inflammatory response-related pathway. The photo-responsive fiber-embedded hydrogels offer a promising strategy for constructing a photo-triggered programmable therapeutic platform for regenerative medicine.
研究领域:
生物材料
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纳米医学
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再生医学
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创面愈合
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药物递送
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生物工程
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高影响因子
Biomaterials Advances
·
2025
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IF 6
Naiyu Wang,Shiqi Kang,Qi Zeng,Wu Xu,Yuanyuan Zhao,Xudong Shi,Ruijun Li
Limited ability of nerve regeneration and the formation of nerve adhesions result to poor outcomes of peripheral nerve injury (PNI) following surgical nerve repair. Currently, there is no efficient therapy for the improvement of functional recovery after surgical repair. Rapamycin (Rapa) has been found useful for promoting nerve regeneration through removing cellular debris at the early stages after PNI. However, its lower oral bioavailability and significant adverse effects limit its clinical application. In this study, we developed a biocompatible nerve wrap based on biocompatible monomethoxy poly (ethylene gly co l)-poly (lactic- co -glycolic acid) (mPEG-PLGA) for the local delivery of Rapa. The Rapa-mPEG-PLGA nerve wrap exhibited a rough surface and good hydrophilicity with strong mechanical strength. In vitro release studies revealed an initial rapid phase within the first 8 days, followed by a stable release about 10 days. The released Rapa remained its bioactivity to induce autophagy and promote cell migration. In a rat model of sciatic nerve transection and immediate repair, the implantation of Rapa-mPEG-PLGA nerve wrap significantly enhanced axonal regeneration and myelination. Furthermore, the nerve wraps effectively prevented the occurrence of nerve adhesions. Improved functional recovery was observed with Rapa-mPEG-PLGA membrane wrap post-surgery 4 weeks and 8 weeks. In summary, the Rapa-loaded mPEG-PLGA nerve wrap promoted nerve regeneration by releasing Rapa at the early stage after injury, and acted as a physical barrier to reduce nerve adhesions. This local dual-action strategy is a promising candidate for clinical translation in the treatment of PNI following surgical repair.
研究领域:
生物医学工程
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神经科学
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药理学
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生物材料
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再生医学
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高影响因子
ACS Applied Bio Materials
·
2024
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IF 4.6
Hao Chen,Xilin Xiong,Yuan Huang,Bo Huang,Xinxin Luo,Qi Ke,Pengyu Wu,Suxiao Wang
The global outbreak of the COVID-19 pandemic has indisputably wreaked havoc on societies worldwide, compelling the scientific community to seek urgently needed therapeutic agents with low-cost and low-side effect profiles. Numerous approaches have been investigated in the quest to prevent or treat COVID-19, but many of them exhibit unwelcome side effects, such as dysfunctional viral immune responses and inflammation. Herein, we present the preparation of solid natural human pulmonary alveolar epithelial cell (ATII) membrane-coated PLGA NPs (PLGA NPs@ATII-M), which demonstrate remarkable affinity and competitiveness to neutralize the SARS-CoV-2 S1 protein-coated NPs (SCMMA NPs–S1), which are employed as a surrogate for coronavirus particles. In addition, we first considered the antifouling properties of these types of NPs, and we found that this membrane-coated NP formulation boasts excellent antifouling capabilities, which serve to protect their neutralization properties out of shielding by protein coronas in blood circulation. Moreover, this formulation is easily prepared and stored with a low-cost profile and exhibits good specificity, high targeting efficiency, and potentially side effect avoiding, thus making it a highly promising candidate for COVID-19 treatment.
研究领域:
药学
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纳米技术
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病毒学
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生物医学工程
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高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Manyu Chen,Jing Wang,Yuhan Liu,Xiaolin Cui,Jie Liang,Ning Lei,Yumei Xiao,Qiguang Wang,Yujiang Fan,Xingdong Zhang
Osteoarthritis (OA), characterized by cartilage degeneration and functional impairment, remains a significant unmet medical need with limited therapeutic options available. While stem cell therapies, particularly those derived from bone marrow mesenchymal stem cells (BMSCs), hold great promise, they are hampered by challenges including cell instability and safety concerns. This study develops and investigates the potential of biomimetic microcarriers (BMSCs-CF@M-PLGA), synthetic cells that encapsulate BMSC paracrine factors within PLGA microspheres and are coated with BMSC membranes. These cells aim to overcome the limitations of conventional stem cell therapies while maintaining their therapeutic efficacy. In vitro experiments demonstrated that BMSCs-CF@M-PLGA significantly enhance chondrocyte proliferation, migration, and extracellular matrix synthesis, attributed to the synergistic action of paracrine factors and the protective properties of the cell membranes. In vivo studies confirmed the therapeutic efficacy of BMSCs-CF@M-PLGA in OA rat models, resulting in improved joint morphology and cartilage structure. Transcriptomic analysis revealed the regulation of extracellular matrix synthesis, cell survival, and inflammation pathways, with a shift towards reduced pro-inflammatory cytokines and increased anti-inflammatory cytokines. This study highlights the encouraging therapeutic potential of BMSCs-CF@M-PLGA, offering enhanced stability, safety, and convenience for OA treatment.
研究领域:
再生医学
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组织工程
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药理学
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骨科
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高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2026
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IF 6
Xia Yin,Bin Chen,Yan Qing Wang,Yan Yan,Qian Ding,Suguro Rinkiko,Yi Chun Zhu,Yi Zhun Zhu
Efficient encapsulating of highly hydrophilic low-molecular-weight compound within poly (D, L-lactic-co-glycolic acid) (PLGA) to obtain microspheres with both excellent drug loading capacity (DL) and encapsulation efficiency (EE) was substantially challenging. This study specifically aimed to enhance both the DL and EE of this hydrophilic low-molecular-weight compound S-propargyl-cysteine (SPRC) while extending its release duration through implementation of the solvent-induced phase separation (SIPS) methodology. S-propargyl-cysteine (SPRC)-loaded PLGA microspheres (SP-MSs) were fabricated using conventional emulsion solvent evaporation techniques (W/O/W and S/O/W) and compared with those prepared via SIPS. The influences of various preparation techniques on critical pharmaceutical properties of sustained-release SP-MSs, including drug loading capacity, encapsulation efficiency, in vitro release profiles, surface-localized drug content, crystal state of SPRC, and microstructural characteristics were also systematically investigated. Microspheres sythesized through SIPS demonstrated a remarkable enhancement in DL, increasing from 0.90% to 9.91%, with the corresponding EE improving dramatically from 17.8% to 99.2%. Furthermore, the SIPS approach effectively mitigated the initial burst release phenomenon commonly observed in polymeric microsphere formulations. In vivo pharmacokinetic studies in Sprague-Dawley rats confirmed the sustained-release profile of the optimized formulation, maintaining stable plasma concentrations for an extended period of seven days. These findings establish SIPS as a superior methodology for encapsulating SPRC within PLGA microspheres, effectively addressing dual challenges of low DL and EE. This investigation provides significant methodological insights for the effective encapsulation of hydrophilic low-molecular-weight therapeutic agents within PLGA-based delivery systems, offering a promising strategy for achieving prolonged sustained-release both in vitro and in vivo . Solvent-induced phase separation was employed to encapsulate highly hydrophilic S-propargyl-cysteine (SPRC) within injectable PLGA microspheres to (i) maximize EE and DL, (ii) suppress the initial burst, and (iii) achieve prolonged, controlled release of SPRC for 7 days both in vitro and in vivo . Download: Download high-res image (93KB) Download: Download full-size image
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2025
·
IF 2.2
Chang Luo,Cheng Kang,Shi Qiu,Weiming Wang,Yiyi Lou,Xiaofei Wang,Ting Zhu
Biodegradable scaffolds have significant potential for directed tissue regeneration in craniofacial and oral applications and bone regeneration. We designed an innovative cerium-altered/collagen-clacked polycaprolactone/poly-lactic-co-glycolic acid (PC/PL) electrospun scaffolds (PC/PL-PD-Ce-CL) to address the deficiencies of existing scaffold materials regarding osteogenic and antimicrobial characteristics. Novel scaffolds were developed by electrospinning a fundamental PCL/PLGA matrix, impregnating in situ reduction with cerium nanoparticles (CeNPs), applying a polydopamine coating, and clacking with collagen. The mechanical tests and scanning electron microscope demonstrated that the distinctive NSs preserved their tensile strength and elasticity modulus post-modification. The cell proliferation CCK-8 assay indicated that the PC/PL-PD-Ce-CL NSs exhibited a superior MG63 cell proliferation and cell adhesion ratio compared to the rest of the NSs. The alkaline phosphatase (ALP) activity and the expression levels of BMP2 and RUNX2 in MG63 cells cultivated on PC/PL-PD-Ce-CL NSs for 7 and 14 days were considerably elevated compared to the controls. The PC/PL-PD-Ce-CL and PC/PL-PD-Ce NSs exhibited a broader antibacterial zone compared to the control NSs, and bacterial fluorescence diminished on the Ce-altered NSs of incubation with S. mutans and S. aureus . Our innovative PC/PL-PD-Ce-CL NSs improved cytocompatibility, osteogenesis, and antibacterial capabilities, demonstrating their promising therapeutic applications for orofacial treatment.
研究领域:
生物材料学
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组织工程学
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口腔医学
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高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 22
·4488-4501
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IF 6.331
Yichen Dou,Jinhui Huang,Xue Xia,Jiawei Wei,Qin Zou,Yi Zuo,Jidong Li,Yubao Li
The ideal scaffold for bone repair should have a hierarchical pore structure and gradient degradation performance to satisfy the uniform adhesion and proliferation of cells in the scaffold at the early stage of implantation, as well as providing space for the subsequent regeneration of bone tissue. To this end, we developed a hierarchical polylactic acid glycolic acid copolymer (PLGA)/nano-hydroxyapatite (n-HA)/gelatin (Gel) (PHG) scaffold with a printed PLGA/n-HA (PH) framework and a Gel network filler for bone regeneration by the combination of 3D printing and freeze-drying technologies. The fabricated PHG scaffold features large front hole size (>1100 μm × 1100 μm) and side hole size (>500 μm) to provide sufficient open space and reliable integrated support for cell and tissue ingrowth. The gelatin network filled in the PH framework played the role of a cell holder just like an extracellular matrix (ECM) in the early stage. In vitro degradation experiments revealed that the gelatin network completely degraded within 5 weeks while the structural integrity of the framework still remained at the 32nd week. The results of cell culture confirmed that the PHG scaffold was more conducive to cell attachment. In vivo assessments in a rat femoral defect model showed that PHG scaffolds were more favored for new bone formation and achieving a tighter bond between the scaffold and the original tissues. The hierarchical PHG scaffold has great application potential in bone tissue engineering and will provide a reference for the model design of bone scaffolds.
研究领域:
生物医学工程
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组织工程
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材料科学
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再生医学
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高影响因子
International Journal of Nanomedicine
·
2023
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IF 8
Liping Zhang,Yuan Xu,Wenjuan Cao,Shibao Xie,Lu Wen,Gang Chen
Background The round window membrane (RWM) functions as the primary biological barrier for therapeutic agents in the inner ear via local application. Previous studies on inner ear nano-drug delivery systems mostly focused on their pharmacokinetics and distribution in the inner ear, but seldom on the interaction with the RWM. Clarifying the transport mechanism of nanoparticulate carriers across RWM will shed more light on the optimum design of nano-drug delivery systems intended for meeting demands for their clinical application.Methods The poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) encapsulating coumarin-6 were prepared by emulsifying solvent evaporation method. We utilized confocal laser scanning microscope (CLSM) in combination with transmission electron microscope to investigate the transport pathway of PLGA NPs in the RWM. Simultaneously, the concentration and time dependence of NPs across the RWM were also determined. The endocytic mechanism of NPs through this membrane interface was classically analyzed by means of various endocytic inhibitors. The intracellular location of NPs into lysosomes was evaluated using CLSM scanning microscope colocalization analysis. The Golgi-related inhibitors were employed to probe into the function of Golgi and endoplasmic reticulum (ER) in the discharge of NPs out of cells.Results PLGA NPs were herein transported through the RWM of a sandwich-like structure into the perilymph via the transcellular pathway. NPs were internalized predominantly via macropinocytosis and caveolin-mediated endocytic pathways. After being internalized, the endocytosed cargos were entrapped within the lysosomal compartments and/or the endoplasmic reticulum/Golgi apparatus which mediated the exocytotic release of NPs.Conclusion For the first time, we showed the translocation itinerary of NPs in RWM, providing a guideline for the rational fabrication of inner ear nanoparticulate carriers with better therapeutic effects.
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高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2022
·Vol. 24
·期 1
·390
·
IF 6.208
Haozhe Cheng,Qian Guo,Hongjian Zhao,Kun Liu,Honglei Kang,Fang Gao,Jianfeng Guo,Xi Yuan,Shuang Hu,Feng Li,Qin Yang,Zhong Fang
Due to the unique physical characteristics of intervertebral disc degeneration (IVDD) and the pathological microenvironment that it creates, including inflammation and oxidative stress, effective self-repair is impossible. During the process of intervertebral disc degeneration, there is an increase in the infiltration of M1 macrophages and the secretion of proinflammatory cytokines. Here, we designed a novel injectable composite hydrogel scaffold: an oligo [poly (ethylene glycol) fumarate]/sodium methacrylate (OPF/SMA) hydrogel scaffold loaded with dual-drug/sustained-release PLGA microspheres containing IL-4 (IL-4-PLGA) and kartogenin (KGN-PLGA). This scaffold exhibited good mechanical properties and low immunogenicity while also promoting the sustained release of drugs. By virtue of the PLGA microspheres loaded with IL-4 (IL-4-PLGA), the composite hydrogel scaffold induced macrophages to transition from the M1 phenotype into the M2 phenotype during the early induced phase and simultaneously exhibited a continuous anti-inflammatory effect through the PLGA microspheres loaded with kartogenin (KGN-PLGA). Furthermore, we investigated the mechanisms underlying the immunomodulatory and anti-inflammatory effects of the composite hydrogel scaffold. We found that the scaffold promoted cell proliferation and improved cell viability in vitro. While ensuring mechanical strength, this composite hydrogel scaffold regulated the local inflammatory microenvironment and continuously repaired tissue in the nucleus pulposus via the sequential release of drugs in vivo. When degenerative intervertebral discs in a rat model were injected with the scaffold, there was an increase in the proportion of M2 macrophages in the inflammatory environment and higher expression levels of type II collagen and aggrecan; this was accompanied by reduced levels of MMP13 expression, thus exhibiting long-term anti-inflammatory effects. Our research provides a new strategy for promoting intervertebral disc tissue regeneration and a range of other inflammatory diseases.Keywords:drug delivery;hydrogel;intervertebral disc degeneration;immune regulation;kartogenin
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Journal of Materials Chemistry B
·
2024
·
IF 6.1
Jie Tan,Zecai Chen,Zhen Xu,Yafang Huang,Lei Qin,Yufeng Long,Jiayi Wu,Hantao Yang,Xuandu Chen,Weihong Yi,Ruiqiang Hang,Min Guan,Huaiyu Wang,Ang Gao,Dazhi Yang
The 3D printed scaffolds constructed from polymers have shown significant potential in the field of bone defect regeneration. However, the efficacy of these scaffolds can be markedly reduced in certain pathological conditions like diabetes, where the altered microenvironment complicates the integration of these polymers with the host tissue. In this study, the bioactivity of 3D-printed PLGA scaffold is augmented through integration of hydroxyapatite, icariin, and small intestine submucosa (SIS), a form of decellularized extracellular matrix (dECM). In vitro and in vivo studies demonstrate that this functionalized scaffold not only provides desirable immunoregulatory effect, but also facilitates angiogenesis and osteogenesis during the subsequent process. This functionalization approach holds significant promise in advancing the treatment of bone defects within the diabetic population, paving a step forward in the application of polymer-based 3D printing technologies in regenerative medicine.
研究领域:
再生医学
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生物医学工程
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组织工程
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糖尿病研究
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生物材料科学
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高影响因子
危险品化学品经营许可证（带存储）