Light and pH dual-degradable triblock copolymer micelles for controlled intracellular drug release.
A novel amphiphilic ABA-type triblock copolymer poly(ethylene glycol)-b-poly(ethanedithiol-alt-nitrobenzyl)-b-poly(ethylene glycol) (PEG-b-PEDNB-b-PEG) is successfully prepared by sequential thiol-acrylate Michael addition polymerization in one pot. PEG-b-PEDNB-b-PEG is designed to have light-cleavable o-nitrobenzyl linkages and acid-labile β-thiopropionate linkages positioned repeatedly in the main chain of the hydrophobic block. The light and pH dual degradation of PEG-b-PEDNB-b-PEG is traced by gel permeation chromatography (GPC). Such triblock copolymer can self-assemble into micelles, which can be used to encapsulate anticancer drug doxorubicin (DOX). Because of the different degradation chemistry of o-nitrobenzyl linkages and β-thiopropionate linkages, DOX can be released from the micelles by two different manners, i.e., light-induced rapid burst release and pH-induced slow sustained release. Confocal laser scanning microscopy (CLSM) results indicated that DOX-loaded micelles exhibited faster drug release in A549 cells after UV irradiation. Furthermore, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) results show that the DOX-loaded micelles under UV light degradation exhibit better anticancer activity against A549 cells than that of the nonirradiated ones.
MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China.
Qiao
Q
Jin
Tongjiang
T
Cai
Haijie
H
Han
Haibo
H
Wang
Yin
Y
Wang
Jian
J
Ji
D000964:Antimetabolites, Antineoplastic / Q000737:chemistry* / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D057930:Click Chemistry; D003692:Delayed-Action Preparations; D004317:Doxorubicin / Q000737:chemistry* / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008823:Micelles; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification; D014466:Ultraviolet Rays
D000964:Antimetabolites, Antineoplastic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D004317:Doxorubicin
drug release; light-degradable; pH-degradable; self-assembly; triblock copolymer