COMPOSITES PART B-ENGINEERING
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2024
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IF 12.7
Guoyang Zhang,Dingyi Shi,Yiyao Wei,Mingqi Wang,Haohan Wang,Zhiqi Lin,Haihan Gao,Weixuan Lin,Hanyi Wang,Yonglin Guo,Yingyu Ge,Yi Lin,Yiwen Jiang,Xiaoyu Yan,Yuhao Kang,Liren Wang,Jinzhong Zhao,Weiyang Ying
Natural small-molecule drugs have promising potential to promote tissue regeneration in various fields. Therefore, maximizing drug efficiency while minimizing potential side effects is imperative. Peiminine, a natural product extracted from natural Fritillaria , is one of small-molecule drugs in the field of bone regeneration due to its good bone-promoting and anti-inflammatory abilities. However, its application is limited by a lack of biological activity, poor biocompatibility at high concentrations, and difficulty in achieving long-term slow-release and therapeutic effects. Extracellular vesicles (EVs) produced by preconditioned cells are considered to have special biological functions, and their potential to further retain, buffer, and transmit drug effects and expand the therapeutic effect has been widely studied. Thus, our study provides a drug-free bioengineering strategy by preconditioning bone marrow mesenchymal stem cells (BMSC) with Peiminine, then EVs, secreted as Peim-EVs, were extracted and combined with a decellularized extracellular matrix (dECM). The final EVs-dECM system with a spatiotemporally controlled release system was formed. In vitro studies demonstrated that Peim-EVs solved the problem of Peiminine biocompatibility and exhibited osteogenic and anti-inflammatory effects, which may be related to PI3K/AKT, MAPK/NF-κB, and Hippo signaling pathways. An in vivo model of rotator cuff injury in rats also showed that EVs-dECM had a good effect on rotator cuff repair. Combined with engineering strategy, this study provides verification and scenario expansion for drug application, especially for drug-free strategies that retain the biological effects of drugs, and has broad significance.
研究领域:
再生医学
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细胞生物学
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生物工程
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2021
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IF 5.268
Ning Wang,Chenyu Liu,Weihe Yao,Hengjun Zhou,Simiao Yu,Hailiang Chen,Weihong Qiao
Constructing highly efficient and multifunctional nanoparticles to overcome the multiple challenges of targeted drug delivery is a new strategy urgently needed in tumor therapy. Here, we synthesized pH-responsive prodrug ( PEG 2K -NH -N- DOX ), GSH-responsive prodrug ( PEG 2K -S-S-CPT ), folate-receptor targeting polymers ( FA-PEG 2K -L8 , FA-PEG 2K -TOS) and T1-enhanced magnetic resonance imaging contrast agents ( Gd-DTPA-N16−16) , used to encapsulate combrestatinA4 (CA4) to prepare multifunctional nanoparticles ( FTDCAG NPs). Unlike other nanoparticles, FTDCAG NPs contains three drugs with the ability to control the release in time and space, which can maximize the effectiveness of precise cancer chemotherapy. We first confirmed that specific binding between FTDCAG NPs and overexpressed folate-receptor cells by flow cytometry and confocal laser scanning microscopy. We then investigated the spatiotemporally controlled release ability of FTDCAG NPs loaded with doxorubicin (DOX), CA4 and camptothecin (CPT). Relative to pH = 7.4, the release efficiency of CA4 in the pH = 6.5 increased by 63.4 %. The first released CA4 is able to destroy the angiogenesis and help tumor cells to be exposed to the remaining FTDCG NPs. After being internalized into the tumor cells, FTDCG NPs is disassembled and the CPT and DOX were released due to the increase of intracellular GSH concentration and the decrease of pH value. Besides, the relaxation time of FTDCAG NPs is 3.86 times that of clinical Gd-DTPA, and the in vitro and vivo T1-weighted imaging is brighter, which can be used to trace the nanoparticles by MRI. Therefore, FTDCAG NPs provide an efficient strategy for the design of multifunctional drug delivery systems for enhancing antitumor efficacy.
研究领域:
纳米医学
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癌症治疗
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药物递送系统
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）