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Folic‐Acid‐Mediated Functionalized Gold Nanocages for Targeted Delivery of Anti‐miR‐181b in Combination of Gene Therapy and Photothermal Therapy against Hepatocellular Carcinoma
Author(s) -
Huang Shengnan,
Duan Shaofeng,
Wang Jing,
Bao Shijin,
Qiu Xiaojing,
Li Chunming,
Liu Ying,
Yan Lijuan,
Zhang Zhenzhong,
Hu Yurong
Publication year - 2016
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.201504912
Subject(s) - nanocages , photothermal therapy , genetic enhancement , folate receptor , materials science , cancer research , gene delivery , in vivo , linker , pegylation , folic acid , microrna , nanotechnology , rational design , hepatocellular carcinoma , combination therapy , cancer , cancer cell , pharmacology , biochemistry , medicine , chemistry , gene , biology , microbiology and biotechnology , computer science , operating system , catalysis
Therapeutic strategies based on modulation of microRNAs (miRNAs) activity hold much promise for cancer therapy, but for clinical applications, the efficient delivery of miRNAs to tumor cells or tumor tissues remains a great challenge. In this work, microRNA‐181b inhibitor (anti‐miR‐181b) is successfully condensed into polyethyleneimine (PEI)‐modified and folate receptor (FR)‐targeted PEGylated gold nanocages (AuNCs). This delivery system is designated as anti‐miR‐181b/PTPAuNCs nanocomplexes (PTPAuNC‐NPs), which begin with chemical modification of AuNCs with SH‐PEG 5000 ‐folic acid (SH‐PEG 5000 ‐FA) and SH‐PEG 5000 through a gold–sulfur bond, followed by conjugating PEI using lipoic acid as a linker. Finally anti‐miR‐181b is condensed via electrostatic interactions. In vitro and in vivo experiments show that PTPAuNC‐NPs can efficiently deliver anti‐miR‐181b into target sites to suppress tumor growth, and considerably decrease tumor volumes in SMMC‐7721 tumor‐bearing nude mice under near‐infrared radiation. All these results suggest that PTPAuNC‐NP gene delivery system with combination of gene therapy and photothermal therapy will be of great potential use in future cancer therapy.