Preparation of a thermo-responsive drug carrier consisting of a biocompatible triblock copolymer and fullerene

Abstract

A triblock copolymer (PEG-b-PUEM-b-PMPC; EUM) comprising poly(ethylene glycol) (PEG), thermo-responsive poly(2-ureidoethyl methacrylate) (PUEM), and poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC) blocks was synthesized via controlled radical polymerization. PEG and PMPC blocks exhibit hydrophilicity and biocompatibility. The PUEM block exhibits an upper critical solution temperature (UCST). PMPC can dissolve hydrophobic fullerenes in water to form a complex by grinding PMPC and fullerene powders. Fullerene-C₇₀ (C₇₀) and EUM were ground in a mortar and phosphate-buffered saline (PBS) was added to synthesize a water-soluble complex (C₇₀/EUM). C₇₀/EUM has a core–shell-corona structure, whose core is a complex of C₇₀ and PMPC, the shell is PUEM, and corona is PEG. The maximum C₇₀ concentration dissolved in PBS was 0.313 g L⁻¹ at an EUM concentration of 2 g L⁻¹. The C₇₀/EUM hydrodynamic radius (R_h) was 34 nm in PBS at 10 °C, which increased due to the PUEM block's UCST phase transition with increasing temperature, and R_h attained a constant value of 38 nm above 36 °C. An anticancer drug, doxorubicin, was encapsulated in the PUEM shell by hydrophobic interactions in C₇₀/EUM at room temperature, which can be released by heating. The generation of singlet oxygen (¹O₂) from C₇₀/EUM upon visible-light irradiation was confirmed using the singlet oxygen sensor green indicator. Water-soluble C₇₀/EUM may be used as a carrier that releases encapsulated drugs when heated and as a photosensitizer for photodynamic therapy.