Folate-mediated and doxorubicin-conjugated poly(ε-caprolactone)-g-chondroitin sulfate copolymers for enhanced intracellular drug delivery

Abstract

The aim of this study was to conjugate an anticancer drug, doxorubicin (DOX) and a folate targeting moiety, folic acid (FA), to self-assembled polycaprolactone (PCL)-graft-chondroitin sulfate (CS) copolymers for enhanced chemotherapy. The PCL-graft-CS copolymer was abbreviated as CP. DOX was conjugated to CP using a bifunctional polyethylene glycol as a spacer (CP-DOX). FA was conjugated to the CP-DOX to yield FA-CP-DOX that could enhance the cellular uptake in folate receptor (FR)-overexpressing cancer cells. The CP-DOX and FA-CP-DOX copolymers were confirmed using ¹H-nuclear magnetic resonance (¹H-NMR) and Fourier transform infrared (FTIR) spectrophotometers. CP-DOX was spherical and FA-CP-DOX was worm-like. The copolymers without DOX were non-cytotoxic against U87 cells. The IC₅₀ value (an inhibitory concentration of 50% cell growth) of FA-CP-DOX was comparable to that of free DOX but much lower than that of CP-DOX against U87 cells 24, 48 and 72 h post incubation. Because of recognition of the FR, the magnificent cellular uptake of FA-CP-DOX into U87 cells was observed using flow cytometry and confocal laser scanning microscopy.