Folate-Conjugated and Dual Stimuli-Responsive Mixed Micelles Loading Indocyanine Green for Photothermal and Photodynamic Therapy

A folic acid targeted mixed micelle system based on co-assembly of poly(ε-caprolactone)-b-poly(methoxytri(ethylene glycol) methacrylate-co-N-(2-methacrylamido)ethyl folatic amide) and poly(ε-caprolactone)-b-poly(diethylene glycol monomethyl ether methacrylate) is developed to encapsulate indocyanine green (ICG) for photothermal therapy and photodynamic therapy. In this study, the use of folic acid is not only for specific cancer cell recognition, but also in virtue of the carboxylic acid on folic acid to regulate the pH-dependent thermal phase transition of polymeric micelles for controlled drug release. The prepared ICG-loaded mixed micelles possess several superior properties such as a preferable thermoresponsive behavior, excellent storage stability, and good local hyperthermia and reactive oxygen species generation under near-infrared (NIR) irradiation. The photototoxicity induced by the ICG-loaded micelles has efficiently suppressed the growth of HeLa cells (folate receptor positive cells) under NIR irradiation compared to that of HT-29, which has low folate receptor expression. Hence, this new type of mixed micelles with excellent features could be a promising delivery system for controlled drug release, effective cancer cell targeting, and photoactivated therapy.