Multifunctional Graphene Oxide Nanodelivery Platform for Breast Cancer Treatment.

Abstract

Breastcancer(BC) has the highest global prevalence among all malignancies in women and the second highest prevalence in the overall population. Paclitaxel(PTX),atricyclicditerpenoid, is effective against BC. However, its poor solubility in water and the allergenicity of its dissolution medium limited itsclinicalapplication. In this work, we established a multifunctional graphene oxide (GO) tumor-targeting drug delivery system using nanosized grapheneoxide(nGO) modified with D-tocopherol polyethylene glycol succinate (TPGS) and arginine-glycine-asparticacid(RGD) for PTX loading. The obtained RGD-TPGS-nGO-PTX was 310.20±19.86 nm in size; the polydispersity index (PDI) and zeta potential were 0.21±0.020 and -23.42 mV, respectively. Themeandrugloading capacityof RGD-TPGS-nGO-PTX was 48.78%. RGD-TPGS-nGO-PTX showed satisfactory biocompatibility and biosafety and had no significant toxic effects on zebrafish embryos. Importantly, it exerted excellent cytotoxicity against MDA-MB-231 cells, reversed multi-drug resistance (MDR) in MCF-7/ADR cells, and showed significant anti-tumor efficacy in tumor-bearing nude mice. These findings strongly suggested that the multifunctional GO tumor-targeting drug delivery system RGD-TPGS-nGO-PTX could be used in clinical settings to improve PTX delivery, reverse MDR and increase the therapeutic efficacy of BC treatment.