Folate-decorated thermoresponsive micelles based on star-shaped amphiphilic block copolymers for efficient intracellular release of anticancer drugs.

In this study, a new type of folate-decorated thermoresponsive micelles based on the star-shaped amphiphilic block copolymer 4s[poly(ε-caprolactone)-b-2s(poly(N-isopropylacrylamide-co-acrylamide)-b'-methoxy poly(ethylene glycol)/poly(ethylene glycol)-folate)] (i.e., 4s[PCL-b-2s(P(NIPAAm-co-AAm)-b'-MPEG/PEG-FA)] (PCIAE-FA)), were developed for the tumor-targeted delivery and temperature-induced controlled release of hydrophobic anticancer drugs. These amphiphilic star copolymers are capable of self-assembling into spherical micelles in aqueous solution with an average diameter of 91 nm. The lower critical solution temperature (LCST) of micelles was around 39.7 °C. The anticancer drug, paclitaxel (PTX), was encapsulated into the micelles. In vitro release studies demonstrated that the drug-loaded delivery system (PTX-PCIAE-FA) is relatively stable at physiologic conditions but susceptible to temperatures above LCST which would trigger the release of encapsulated drugs. The cytotoxicity studies showed that the PTX transported by these micelles was higher than that by the commercial PTX formulation Tarvexol(®). The efficacy of this thermoresponsive drug delivery system was also evaluated at temperatures above the LCST; the results demonstrated that the cellular uptake and the cytotoxicity of PTX-loaded micelles increase prominently. These results indicate that these thermoresponsive micelles may offer a very promising carrier to improve the delivery efficiency and cancer specificity of hydrophobic chemotherapeutic drugs.