A novel truncated basic fibroblast growth factor fragment-conjugated poly (ethylene glycol)-cholesterol amphiphilic polymeric drug delivery system for targeting to the FGFR-overexpressing tumor cells.

Targeted uptake of therapeutic nanoparticles in tumor cells-specific manner represents a potentially powerful technology in cancer therapy. In present study, we proposed a drug delivery system formulated with biocompatible and biodegradable cholesterol-block-poly (ethylene glycol) (Chol-PEG(2000)-COOH) polymer. And the surface of the polymer was chemically linked with truncated bFGF fragments (tbFGF). The tbFGF could recognize fibroblast growth factor receptors (FGFR) that are highly expressed by a variety of human cancer cells. The micelles had a size distribution of about 10-50 nm and significantly enhanced the cytotoxicity of paclitaxel to LL/2 cells as demonstrated by MTT test (IC₅₀=0.21 μg/mL for tbFGF conjugated Chol-PEG(2000)-COOH micelles (tbFGF-M-PTX) versus 26.43 μg/mL for free paclitaxel, respectively). Flow cytometry revealed the cellular uptake of rhodamine B encapsulated in the tbFGF-conjugated micelles was increased by 6.6-fold for HepG2, 6.2-fold for A549, 2.9-fold for C26 and 2.7-fold for LL/2 tumor cells, respectively, compared with micelles without tbFGF. The fluorescence spectroscopy images further demonstrated that the tbFGF conjugated micelles could specifically bind to the tumor cells that over-expressed FGFRs and then release rhodamine B into the cytoplasm. Our results suggest the tbFGF conjugated Chol-PEG(2000)-COOH micelles have great potential application for tumor targeting therapy.