Transferrin functionalized chitosan-PEG nanoparticles for targeted delivery of paclitaxel to cancer cells.

ABSTRACT

The present investigation was aimed to utilize the stealth property of polyethylene glycol (PEG) modified chitosan nanoparticles (NPs) and active targeting function of transferrin (Tf) by transferrin receptor-mediated endocytosis to promote drug delivery to cancer cells. Paclitaxel (PTX) loaded nanoparticles (PTX-NP) were prepared by solvent evaporation method; PEGylation was carried out by coupling amine group present on the surface of NPs with hydroxyl group present on the PEG (NP-PEG). Tf conjugation was carried out by coupling carboxylic group present on the surface of ligand and hydroxyl group present on the PEG (NP-PEG-Tf). The uptake of NP-PEG-Tf into cancer cells was found to be higher as compared to non-targeted NPs. Compared with free PTX, PTX-NPs and PTX-NPs-PEG, the PTX-NPs-PEG-Tf demonstrated higher cytotoxicity to human Non-Small Cell Lung cancer cell lines (HOP-62), higher intracellular uptake especially in nuclei and lower hemolytic toxicity. Tf conjugated NPs showed increased retention time in the lungs as well as in blood. These findings indicate that Tf conjugated PEGylated nanoparticles are promising nanoconstructs for the delivery of anti-cancer drugs to cancer cells.