Premium
Hierarchical Tumor Microenvironment‐Responsive Nanomedicine for Programmed Delivery of Chemotherapeutics
Author(s) -
Wang Sheng,
Yu Guocan,
Wang Zhantong,
Jacobson Orit,
Tian Rui,
Lin LiSen,
Zhang Fuwu,
Wang Jing,
Chen Xiaoyuan
Publication year - 2018
Publication title -
advanced materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 10.707
H-Index - 527
eISSN - 1521-4095
pISSN - 0935-9648
DOI - 10.1002/adma.201803926
Subject(s) - nanomedicine , materials science , drug delivery , ethylene glycol , camptothecin , in vivo , tumor microenvironment , cancer research , methacrylate , pharmacology , nanoparticle , nanotechnology , chemistry , medicine , tumor cells , copolymer , biochemistry , biology , microbiology and biotechnology , organic chemistry , composite material , polymer
Abstract Nanomedicines have been demonstrated to have passive or active tumor targeting behaviors, which are promising for cancer chemotherapy. However, most nanomedicines still suffer from a suboptimal targeting effect and drug leakage, resulting in unsatisfactory treatment outcome. Herein, a hierarchical responsive nanomedicine (HRNM) is developed for programmed delivery of chemotherapeutics. The HRNMs are prepared via the self‐assembly of cyclic Arg‐Gly‐Asp (RGD) peptide conjugated triblock copolymer, poly(2‐(hexamethyleneimino)ethyl methacrylate)‐poly(oligo‐(ethylene glycol) monomethyl ether methacrylate)‐poly[reduction‐responsive camptothecin] (PC7A‐POEG‐PssCPT). In blood circulation, the RGD peptides are shielded by the POEG coating; therefore, the nanosized HRNMs can achieve effective tumor accumulation through passive targeting. Once the HRNMs reach a tumor site, due to the hydrophobic‐to‐hydrophilic conversion of PC7A chains induced by the acidic tumor microenvironment, the RGD peptides will be exposed for enhanced tumor retention and cellular internalization. Moreover, in response to the glutathione inside cells, active CPT drugs will be released rapidly for chemotherapy. The in vitro and in vivo results confirm effective tumor targeting, potent antitumor effect, and reduced systemic toxicity of the HRNMs. This HRNM is promising for enhanced chemotherapeutic delivery.