Abstract A31: Cyclic NGR peptide functionalized PEG-PLGA nanoparticles as dual-targeting carrier for site specific antitumor drug delivery

Abstract

Abstract CD13 receptors are abundantly overexpressed in tumor cells as well as in neovasculature. The polymeric nanoparticles (NPs) as the nanomodules for anticancer drug carriers are well known. Nowadays, targeted delivery options are becoming a fascinating approach, so CD13 receptors was selected as a targeted site and NPs as a delivery system. By combining all the issue, a cyclic NGR (cNGR) peptide as a ligand was coupled on the terminal end of polyethylene glycol-b-poly(lactic-co-glycolic acid) (PEG-b-PLGA) and prepared the dual targeted polymeric NPs (cNGR-PEG-PTX-NPs) in order to enhance the intracellular delivery of anticancer drug to the tumor cells and tumor endothelial cells via ligand-receptor interaction. In-vitro cytotoxicity studies confirmed that the presence of cNGR enhanced the cytotoxic efficiency by 2.8 folds in human umbilical vein endothelial (HUVEC) cells, while cytotoxicity was improved by 2.6 folds in human fibrosarcoma (HT-1080) cells as compared to non-specific stealth NPs. Compared with other tested NPs, cNGR-PEG-PTX-NPs revealed more cytotoxicity by inducing more apoptosis, higher cell uptake and more G2/M phase arrest. The tumor volume inhibition rate was 59.7% in case of cNGR-PEG-PTX-NPs that was comparatively more with other formulations, indicating that cNGR-PEG-PTX-NPs could more effectively inhibit tumor growth. As a consequence, the cNGR-PEG-PTX-NPs play a key role in enhancing tumor therapeutic efficiency for treatment of CD13 receptor specific solid tumor. Citation Format: Dr. Madhu Gupta, Sr., Dr. Vikas Sharma, Prof. G.P. Agrawal, Prof. S.P. Vyas. Cyclic NGR peptide functionalized PEG-PLGA nanoparticles as dual-targeting carrier for site specific antitumor drug delivery. [abstract]. In: Proceedings of the AACR Special Conference: Advances in Brain Cancer Research; May 27-30, 2015; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2015;75(23 Suppl):Abstract nr A31.