Synthesis of Photo- and pH Dual-Sensitive Amphiphilic Copolymer PEG43-b-P(AA76-co-NBA35-co-tBA9) and Its Micellization as Leakage-Free Drug Delivery System for UV-Triggered Intracellular Delivery of Doxorubicin

详细信息    查看全文

• 作者：Xubo Zhao ; Mingzhu Qi ; Shuo Liang ; Kun Tian ; Tingting Zhou ; Xu Jia ; Jiagen Li ; Peng Liu
• 刊名：ACS Applied Materials & Interfaces
• 出版年：2016
• 出版时间：August 31, 2016
• 年：2016
• 卷：8
• 期：34
• 页码：22127-22134
• 全文大小：504K
• 年卷期：0
• ISSN：1944-8252

文摘

Novel photo- and pH dual-sensitive amphiphilic copolymers containing photolabile o-nitrobenzyl (NB) groups were designed via combination of ATRP, hydrolyzation, and simple esterification reaction and self-assembled into stimuli-regulated amphiphilic micelles in aqueous solution. On the basis of the optimization of the morphology and particle size of the micelles via modulating the number of the photocleavable o-nitrobenzyl acrylate (NBA) units, the unique ones assembled from PEG₄₃-b-P(AA₇₆-co-NBA₃₅-co-tBA₉) with an average hydrodynamic diameter (D_h) of 163 nm was selected as a potential drug delivery system (DDS) for UV-triggered delivery of doxorubicin (DOX). The micelles possessed a favorable drug-loading capacity (DLC) of 27.5%, with the hydrodynamic diameter of 213 nm after DOX-loading. Most importantly, the DOX-loaded PEG₄₃-b-P(AA₇₆-co-NBA₃₅-co-tBA₉) micelles exhibited a cumulative DOX release ratio of only 3.69% in the simulated physiological medium within 6 days without UV-irradiation, indicating their potential as leakage-free DDS. As in the acidic media mimicking the tumor microenvironment, a high cumulative DOX release ratio of 74.70% was achieved within 6 days after UV-irradiation for 20 min, showing a sustained release behavior. Under UV-irradiation, the photolabile o-nitrobenzyl moieties were cleaved off, the amphiphilic copolymer transformed into a water-soluble polymer, favoring the metabolism of drug carriers, and the micelles were demicellized to accelerate the drug release in a triggered or on-demand manner.