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基于磷脂基紫杉醇纳米前药的抗肿瘤应用研究

Phospholipid-hitchhiked Paclitaxel Nanoprodrugs for Tumor Treatment
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摘要 载体材料是影响药物体内递送效率和抗肿瘤活性的重要因素.本文应用2种不同结构的磷脂材料,包括聚乙二醇修饰的磷脂酰乙醇胺DSPE-PEG和磷脂酰胆碱DPPC,作为载体包裹紫杉醇二聚体(PTX_(2)-SS),制备了紫杉醇纳米颗粒.相比于DPPC,DSPE-PEG作为载体有利于得到均匀的纳米剂型.同时测定了DSPE-PEG作为载体制备的PTX_(2)-SS@DSPE-PEG NPs(DeP NPs)在稳定性、细胞毒性、体内分布和抗肿瘤疗效方面的表现.该工作为研发疏水药物的磷脂型载体提供了一个重要的参考. Carriers play crucial roles in improving the drug delivery efficacy and antitumor activity.Here,two kinds of phospholipid-based carriers,including PEGylated phosphatidyl ethanolamine DSPE-PEG and phosphatidyl choline DPPC,were leveraged to encapsulate dimeric paclitaxel prodrugs to obtain the formulations.The impact of phospholipid-based carriers on the colloidal stability,cytotoxicity,bio-distribution and antitumor efficacy was systemically investigated.Compared with DPPC,DSPE-PEG could form uniform nanoformulations(DeP NPs).The average particle size and zeta-potential of DeP NPs were determined to be 201.1 nm and−13.8 mV,respectively,by dynamic light scattering(DLS).The transmission electron microscopy(TEM)images confirmed their well-defined nanostructures.DeP NPs could remain stable in solutions containing 5%glucose,10%FBS,and RPMI-1640 without serum.The hydrophobic interaction dominates the assembly of DSPE-PEG with PTX prodrug.Upon treated with 10 mmol/L H_(2)O_(2),DeP NPs exhibited the oxidative responsive PTX release.DeP NPs could effectively be internalized by tumor cells,and exhibited more potent cytotoxicity towards cancer cells compared with normal cells.Furthermore,DeP NPs possessed good accumulation of drug at tumor sites and desirable antitumor performance.Our work provides valuable insight into the construction of phospholipid-based carriers material to deliver hydrophobic drugs.
作者 姚秀敏 郝登远 裴晴 谢志刚 景遐斌 Xiu-min Yao;Deng-yuan Hao;Qing Pei;Zhi-gang Xie;Xia-bin Jing(State Key Laboratory of Polymer Physics and Chemistry,Changchun Institute of Applied Chemistry,Chinese Academy of Sciences,Changchun 130022;School of Applied Chemistry and Engineering,University of Science and Technology of China,Hefei 230026)
出处 《高分子学报》 SCIE CAS CSCD 北大核心 2023年第5期708-719,共12页 Acta Polymerica Sinica
基金 国家自然科学基金(基金号52203199,51973214) 吉林省自然科学基金(基金号YDZJ202101ZYTS013)资助项目.
关键词 磷脂 紫杉醇 二聚体前药 纳米药物 化疗 Phospholipid Paclitaxel Dimeric prodrug Nanodrugs Chemotherapy
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