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生物可还原纳米胶囊用于叶酸辅助靶向和有效的肿瘤特异性化疗。

Bioreducible nanocapsules for folic acid-assisted targeting and effective tumor-specific chemotherapy.

机构信息

National Engineering Research Center for Biomaterials, Sichuan University, Chengdu.

College of Materials Science and Engineering, Nanjing Tech University, Nanjing, P.R. China.

出版信息

Int J Nanomedicine. 2018 Jan 31;13:653-667. doi: 10.2147/IJN.S149458. eCollection 2018.

DOI:10.2147/IJN.S149458
PMID:29440892
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5798557/
Abstract

INTRODUCTION

Increasing demands in precise control over delivery and functionalization of therapeutic agents for tumor-specific chemotherapy have led to a rapid development in nanocarriers. Herein, we report a nanocapsule (NC) system for tumor-oriented drug delivery and effective tumor therapy.

MATERIALS AND METHODS

Functionalized hyaluronan is utilized to build up the NC shells, in which bioreduction cleavable sites, targeting ligand folic acid (FA), and zwitterionic tentacles are integrated.

RESULTS

The hollow NCs obtained (~50 nm in diameter) showed well-defined spherical shell structures with a shell thickness of ~8 nm. These specially designed NCs (doxorubicin [DOX]/FA-Z-NCs) with high drug encapsulation content exhibited good biocompatibility in vitro and fast intracellular drug release behavior mediated by intracellular glutathione.

CONCLUSION

Cellular uptake tests demonstrated rapid uptake of these functionalized NCs and effective escape from endosomes. Antitumor efficacy of the DOX/FA-Z-NCs was confirmed by the significant tumor growth inhibition effect as well as greatly reduced side effects, in contrast with those of the free drug DOX hydrochloride.

摘要

简介

为了实现对肿瘤特异性化疗中治疗剂递释和功能化的精确控制，人们对纳米载体的研究迅速发展。本文报道了一种用于靶向药物递送和有效肿瘤治疗的纳米胶囊（NC）系统。

材料与方法

利用功能化透明质酸构建 NC 壳，其中整合了生物还原可裂解部位、靶向配体叶酸（FA）和两性离子触手。

结果

所得的中空 NC（直径约 50nm）具有良好的球形壳层结构，壳层厚度约为 8nm。这些经过特殊设计的 NC（阿霉素[DOX]/FA-Z-NCs）具有较高的药物包封率，在体外表现出良好的生物相容性和由细胞内谷胱甘肽介导的快速细胞内药物释放行为。

结论

细胞摄取试验表明，这些功能化 NC 具有快速的摄取能力，并能有效从内涵体中逃逸。与游离药物盐酸多柔比星（DOX hydrochloride）相比，DOX/FA-Z-NCs 的抗肿瘤功效得到了证实，其具有显著的肿瘤生长抑制作用和大大降低的副作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b094/5798557/3d4182d32a7a/ijn-13-653Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b094/5798557/57026cc9633f/ijn-13-653Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b094/5798557/61280e60400e/ijn-13-653Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b094/5798557/5cd595e9ad5c/ijn-13-653Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b094/5798557/b8af5b19f850/ijn-13-653Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b094/5798557/9344650f8382/ijn-13-653Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b094/5798557/45e509f7d01c/ijn-13-653Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b094/5798557/32ff415c88ef/ijn-13-653Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b094/5798557/0c53dfcdf06f/ijn-13-653Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b094/5798557/d7e0af5e437f/ijn-13-653Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b094/5798557/3d4182d32a7a/ijn-13-653Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b094/5798557/57026cc9633f/ijn-13-653Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b094/5798557/61280e60400e/ijn-13-653Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b094/5798557/5cd595e9ad5c/ijn-13-653Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b094/5798557/b8af5b19f850/ijn-13-653Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b094/5798557/9344650f8382/ijn-13-653Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b094/5798557/45e509f7d01c/ijn-13-653Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b094/5798557/32ff415c88ef/ijn-13-653Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b094/5798557/0c53dfcdf06f/ijn-13-653Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b094/5798557/d7e0af5e437f/ijn-13-653Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b094/5798557/3d4182d32a7a/ijn-13-653Fig10.jpg

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