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功能化聚合物二醛糊精网络包覆的介孔二氧化硅纳米粒子用于pH/谷胱甘肽双控药物释放。

Functional polymeric dialdehyde dextrin network capped mesoporous silica nanoparticles for pH/GSH dual-controlled drug release.

作者信息

Chen Chao, Sun Wen, Yao Wenji, Wang Yibing, Ying Hanjie, Wang Ping

机构信息

State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing, Biomedical Nanotechnology Center, School of Biotechnology, East China University of Science and Technology Shanghai 200237 People's Republic of China

State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University Puzhu South Road Nanjing 211816 People's Republic of China

出版信息

RSC Adv. 2018 Jun 7;8(37):20862-20871. doi: 10.1039/c8ra03163k. eCollection 2018 Jun 5.

Abstract

Multi-stimulation responsive nanomaterial-based drug delivery systems promise enhanced therapeutic efficacy in cancer therapy. This work examines a smart pH/GSH dual-responsive drug delivery system by using dialdehyde dextrin (DAD) end-capped mesoporous silica nanoparticles (MSNs). Specifically, DAD was applied as a "gatekeeper polymer" agent to seal drug loads inside the mesoporous of MSNs a pH-sensitive Schiff bond, whereas the formed DAD polymer shells were further cross-linked by GSH-sensitive disulfide bonds. Results revealed that the DAD gatekeeper polymer could tightly close the mesopores of MSNs to control premature drug release under physiological conditions and respond to acidic and GSH conditions to release the trapped drugs. Significantly, fluorescent microscopy observation and cytotoxicity studies indicated that drug-loaded nanoparticles could be rapidly internalized through a passive targeting effect to inhibit cancer growth. Taken together, these polymer-modified pH/GSH dual-responsive MSNs could be used as promising candidates for "on-demand" anticancer drug delivery applications.

摘要

基于多刺激响应纳米材料的药物递送系统有望在癌症治疗中提高治疗效果。这项工作通过使用端接二醛糊精(DAD)的介孔二氧化硅纳米颗粒(MSN)来研究一种智能pH/谷胱甘肽(GSH)双响应药物递送系统。具体而言,DAD作为一种“守门人聚合物”试剂,通过pH敏感的席夫碱将药物负载密封在MSN的介孔内,而形成的DAD聚合物壳层则通过GSH敏感的二硫键进一步交联。结果表明,DAD守门人聚合物可以紧密关闭MSN的介孔,以控制生理条件下药物的过早释放,并对酸性和GSH条件作出响应以释放被捕获的药物。重要的是,荧光显微镜观察和细胞毒性研究表明,载药纳米颗粒可通过被动靶向效应迅速内化以抑制癌症生长。综上所述,这些聚合物修饰的pH/GSH双响应MSN可作为“按需”抗癌药物递送应用的有前途的候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a74/9080849/c29ce8c263e3/c8ra03163k-s1.jpg

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