Co-delivery of paclitaxel and tetrandrine via iRGD peptide conjugated lipid-polymer hybrid nanoparticles overcome multidrug resistance in cancer cells

• DOI: 10.1038/srep46057
• Publication Date: 2017-05-04T09:10:20Z
• Authors: Jinming Zhang; Lu Wang; Hon Fai Chan; Wei Xie; Sheng Chen; Chengwei He; Yitao Wang; Meiwan Chen
• Keywords: Tetrandrine; Internalization

Abstract One of the promising strategies to overcome tumor multidrug resistance (MDR) is deliver anticancer drug along with P-glycoprotein (P-gp) inhibitor simultaneously. To enhance cancer cellular internalization and implement controlled release, herein an iRGD peptide-modified lipid-polymer hybrid nanosystem (LPN) was fabricated coload paclitaxel (PTX) tetrandrine (TET) at a precise combination ratio. In this co-delivery system, PTX covalently conjugated poly ( D,L -lactide-co-glycolide) polymeric core by redox-sensitive disulfide bond, while TET physically capsulated spontaneously for aim suppress P-gp in advance earlier released cells. As result, PTX+TET/iRGD LPNs core-shell structure possessed high loading efficiency, stability release profiles. Owing enhanced uptake suppression mediated TET, significantly more accumulated A2780/PTX cells treated than either free drugs or non-iRGD modified LPNs. expected, presented highest cytotoxicity against effectively promoted ROS production, apoptosis cell cycle arrests particularly. Taken together, system demonstrated great promise as potential treatment MDR-related tumors based on synergistic effects inhibition, endocytosis intracellular sequentially release.