Folate-conjugated amphiphilic star-shaped block copolymers as targeted nanocarriers.

Folate (FA)-conjugated star-shaped copolymer was prepared as a targeted carrier for anticancer drug delivery by ring-opening polymerization of L-lactide using pentaerythritol (PTL) as an initiator, followed by conjugation with methoxy poly(ethylene glycol) (MPEG) and FA-poly(ethylene glycol) (FA-PEG). The resulting amphiphilic star-shaped copolymer was shaped into drug-loaded micelles, and the achieved micelles had an average size of around 146 nm in diameter. It was found that the sustained release time of model drug (indomethacin, IMC) from some selected micelles could reach around 40 h. In comparison with linear poly(L-lactic acid)-block-methoxy poly(ethylene glycol) copolymer (PLA-MPEG), the stability of the star-shaped pentaerythritol-co-poly(L-lactic acid)-block-[methoxy poly(ethylene glycol) and FA-poly(ethylene glycol)] (PTL-PLA-MPEG/PEG-FA) micelle was significantly improved because of the lower critical micelle concentration (CMC). The specificity of PTL-PLA-MPEG/PEG-FA targeting cancer cells was demonstrated by intracellular uptake of PTL-PLA-MPEG/PEG-FA and PTL-PLA-MPEG using HeLa human cervical cancer cells. After 2 h in vitro incubation, a significant intracellular uptake for PTL-PLA-MPEG/PEG-FA over PTL-PLA-MPEG was observed by using inverted fluorescence microscope and flow cytometry. These results suggested that PTL-PLA-MPEG/PEG-FA polymeric micelle could be a potentially useful carrier for delivering selected drugs to FA-receptor positive cancer cells.