EphA2 Targeting Pegylated Nanocarrier Drug Delivery System for Treatment of Lung Cancer |
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Authors: | Apurva R Patel Mahavir Chougule Mandip Singh |
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Institution: | 1. College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, Florida, 32307, USA 2. College of Pharmacy, University of Hawaii at Hilo, Hilo, Hawaii, 96720, USA
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Abstract: | 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. |
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