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Programmed Multiresponsive Vesicles for Enhanced Tumor Penetration and Combination Therapy of Triple‐Negative Breast Cancer
Author(s) -
Zhou Fangyuan,
Feng Bing,
Wang Tingting,
Wang Dangge,
Meng Qingshuo,
Zeng Jianfeng,
Zhang Zhiwen,
Wang Siling,
Yu Haijun,
Li Yaping
Publication year - 2017
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.201606530
Subject(s) - doxorubicin hydrochloride , nanomedicine , prodrug , materials science , liposome , photosensitizer , doxorubicin , photodynamic therapy , triple negative breast cancer , nanocarriers , ethylene glycol , polyethylene glycol , pheophorbide a , drug delivery , cancer research , biophysics , pharmacology , nanotechnology , breast cancer , chemistry , chemotherapy , medicine , cancer , nanoparticle , biochemistry , biology , organic chemistry , surgery
Nanomedicine is a promising approach for combination chemotherapy of triple‐negative breast cancer (TNBC). However, the therapeutic efficacy of nanoparticulate drugs is suppressed by a series of biological barriers. The authors herein present a programmed stimuli‐responsive liposomal vesicle to overcome the sequential barriers for enhanced TNBC therapy. The intelligent vesicles are engineered by integrating an enzyme‐cleavable polyethylene glycol (PEG) corona, a light‐responsive photosensitizer pheophorbide a (PPa), and a temperature‐sensitive liposome (TSL) into a single nanoplatform. The resultant enzyme, light, and temperature multisensitive liposome (ELTSL) is sequentially coloaded with a lipophilic oxaliplatin prodrug of hexadecyl‐oxaliplatin carboxylic acid (HOC) and hydrophilic doxorubicin hydrochloride (DOX). Dual drug‐loaded ELTSL displays enhanced tumor penetration and increased cellular uptake upon matrix metalloproteinase 2 mediated cleavage of the PEG corona. Under NIR laser irradiation, PPa induces mild hyperthermia effect to trigger ultrafast drug release in the tumor cells. In combination with PPa‐mediated photodynamic therapy, HOC and DOX coloaded ELTSL show significantly improved antitumor efficacy than monotherapy. Given the clinically translatable potential of the liposomal vesicles, ELTSL might represent a promising nanoplatform for combination TNBC therapy.