Construction of hydroxypropyl-β-cyclodextrin copolymer nanoparticles and targeting delivery of paclitaxel

A novel amphiphilic copolymer with p-maleimidophenyl isocyanate- hydroxypropyl-β-cyclodextrin-polylactide-1,2-dipalmitoyl-sn-glycero-3- phosphoethanolamine to generate copolymer nanoparticles (NPs) has been designed. In order to develop an active targeting system, integrin α _vβ ₃-specific targeting peptide cyclo(Arg-Gly-Asp-D- Phe-Cys), cRGD, was conjugated to the surface of NPs (NPs-RGD). These NPs were used to encapsulate anti-tumor drug, paclitaxel. The resulting NPs exhibited high drug-loading capacity and controlled drug release in vitro at acidic pH. In vitro cytotoxicity assay demonstrates that paclitaxel-loaded NPs-RGD significantly inhibited B16 tumor cell (high α _vβ ₃) proliferation relative to free paclitaxel and paclitaxel-loaded NPs at high concentrations. Paclitaxel-loaded NPs-RGD localized mainly in lysosomes in B16 cells as revealed by confocal microscopy. These results suggest a novel strategy for fabrication-functionalizing hydroxypropyl-β- cyclodextrin copolymer nanoparticles for targeting delivery of paclitaxel to integrin α _vβ ₃-rich tumor cells. These nanocarriers can be readily extended to couple other bioactive molecules for active targeting and delivery of various chemotherapeutic drugs.