Single-Layer Assembly of Multifunctional Carboxymethylcellulose on Graphene Oxide Nanoparticles for Improving in Vivo Curcumin Delivery into Tumor Cells.

Abstract

Nanodrug delivery systems are considered as promising therapeutic platforms to convey drugs to tumor cells. In this study, a single layer of carboxymethylcellulose (CMC) and poly N-vinylpyrrolidone (PVP) was cross-linked through disulfide bond and deposited on graphene oxide nanoparticles (GO NPs) using layer-by-layer technique. Overexpression of folate receptors on tumor cells is a great hallmark for drug delivery systems; though the NPs were functionalized by monoclonal folic acid antibody (FA) using polyethylene glycol (PEG) as linker. The mean diameter of synthesized nanoparticles was 60 nm. Curcumin was encapsulated within CMC layer with high encapsulation capacity of 94%. In vitro investigation showed 87% curcumin release at simulated tumor environment. Curcumin loaded FA modified CMC/PVP GO NPs showed high inhibition of 76 and 81% against Saos2 and MCF7 cell lines in vitro. In vivo investigations on 4T1 bearing breast cancer mice model exhibited 76% antitumor efficiency via active targeting mechanism of folate mediated transport without any significant side effect. Immunohistochemistry and immunofluorescence analyses showed enhanced antiangiogenesis, apoptosis and tumor growth inhibition.