Zwitterionic light-responsive polymeric micelles for controlled drug delivery

Abstract

Novel amphiphilic light-responsive block copolymer spiropyran-poly(2-methacryloyloxyethyl phosphorylcholine) (SP-PMPC) was reported and used as smart drug nanocarriers. SP-PMPC was easily synthesized via atom transfer radical polymerization (ATRP) of 2-methacryloyloxyethyl phosphorylcholine (MPC) using 2-bromo-2-methylpropanoate-ethyl-3′,3′-dimethyl-6-nitrospiro (2H-1-benzopyran-2,2′-indoline) (SP-Br) as initiator. SP-PMPC can self-assemble to micelles with relatively low critical micelle concentration (CMC) value (0.037 mg mL−1). Because of the reversible photochemical isomerization of hydrophobic spiropyran (SP) to hydrophilic merocyanine (MC), the self-assembly and disassembly of SP-PMPC micelles can be well controlled by an external light source, which was proved by ultraviolet-visible light (UV–vis) spectrometry, dynamic light scattering (DLS), and transmission electron microscopy (TEM). The hydrophobic anticancer drug doxorubicin (DOX) can be encapsulated into micelles. In vitro drug release studies showed that the release of DOX was accelerated in the presence of UV irradiation (λ = 365 nm) when compared to similar systems without UV irradiation treatment. The SP-PMPC micelles exhibited superior biocompatibility as measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay owing to the stealth phosphorylcholine outer shell. Moreover, the DOX-loaded SP-PMPC micelles under UV irradiation exhibited better anticancer activity than that of the nonirradiated ones.