A PEGylated megamer-based microRNA delivery system activatable by stepwise microenvironment stimulation

Wangteng Wu; Qida Hu; Meng Wang; Shiyi Shao; Xinyu Zhao; Hongzhen Bai; Junming Huang; Guping Tang; Tingbo Liang

doi:10.1039/c9cc03846a

A PEGylated megamer-based microRNA delivery system activatable by stepwise microenvironment stimulation

Chem Commun (Camb). 2019 Aug 14;55(63):9363-9366. doi: 10.1039/c9cc03846a. Epub 2019 Jul 18.

Authors

Wangteng Wu¹, Qida Hu², Meng Wang², Shiyi Shao², Xinyu Zhao², Hongzhen Bai³, Junming Huang², Guping Tang³, Tingbo Liang⁴

Affiliations

¹ Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. liangtingbo@zju.edu.cn and Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou 310028, China. tangguping@zju.edu.cn.
² Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. liangtingbo@zju.edu.cn.
³ Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou 310028, China. tangguping@zju.edu.cn.
⁴ Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. liangtingbo@zju.edu.cn and The Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou 310003, China and Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou 310003, China.

PMID: 31317136
DOI: 10.1039/c9cc03846a

Abstract

We developed a biodegradable, oncosensitive, megamer-based delivery system for miRNA therapy. The miRNA nanotherapeutics, activatable by stepwise stimulation of acidity and reduction mimicking tumor microenvironment, efficiently improve liver-specific miR-122 expression, increasing the possibility of translational application of miR-122 therapy against liver cancer.

MeSH terms

Animals
Cell Line, Tumor
Dendrimers / chemistry
Drug Carriers / chemistry*
Humans
Liver Neoplasms / drug therapy
Liver Neoplasms / pathology
Mice
Mice, Nude
MicroRNAs / chemistry*
MicroRNAs / metabolism
MicroRNAs / therapeutic use
Nanoparticles / chemistry*
Polyethylene Glycols / chemistry*
Transplantation, Heterologous

Substances

Dendrimers
Drug Carriers
MIRN122 microRNA, human
MicroRNAs
PAMAM Starburst
Polyethylene Glycols