EphA2 targeting pegylated nanocarrier drug delivery system for treatment of lung cancer.

PURPOSE: Evaluation of tumor targeting pegylated EphA2 peptide coated nanoparticles (ENDDs) of a novel anticancer agent DIM-C-pPhC6H5 (DIM-P) and Docetaxel (DOC) and investigate its antitumor activity and potential for treatment of lung cancer. METHODS: Nanoparticles were prepared with DIM-P and DOC (NDDs) using Nano-DeBEE. ENDDs were prepared by conjugating NDDs with 6His-PEG2K-EphA2 peptide and characterized for physicochemical properties, binding assay, cytotoxicity, cellular uptake studies, drug release and pharmacokinetic parameters. Anti-tumor activity of ENDDs was evaluated using a metastatic H1650 and orthotopic A549 tumor models in nude mice and tumor tissue were analyzed by RT-PCR and immunohistochemistry. RESULTS: Particle size and entrapment efficiency of ENDDs were 197 ± 21 nm and 95 ± 2%. ENDDs showed 32.5 ± 3.5% more cellular uptake than NDDs in tumor cells. ENDDs showed 23 ± 3% and 26 ± 4% more tumor reduction compared to NDDs in metastatic and orthotopic tumor models, respectively. In-vivo imaging studies using the Care stream MX FX Pro system showed (p < 0.001) 40-60 fold higher flux for ENDDs compared to NDDs at tumor site. CONCLUSIONS: The results emanating from these studies demonstrate anti-cancer potential of DIM-P and the role of ENDDs as effective tumor targeting drug delivery systems for lung cancer treatment.