Facile designed poly(lactic-co-glycolic acid)-containing nano-platform carried dual drug system to improve progressive combination cancer therapy against human osteosarcoma cells

Abstract

We have designed a methodology to achieve treatment-actuated modifications in a tumor microenvironment by utilizing synergistic activity between two potential anticancer drugs. Dual drug delivery of Sorafenib (Sf) along with Cisplatin (Pt) exhibits a great anti-cancer potential, as Sf enhances the effect of Pt treatment of human osteosarcoma cells by providing microenvironment stability. However, encapsulation of Sf and Pt obsessed by poly(lactic-co-glycolic acid (PLGA)-based nanoparticles (PLGA-NPs) is incompetent owing to unsuitability between the binary free Sf and Pt moieties and the polymeric system. Now, we display that Pt can be prepared by hydrophobic covering of the drug centers with dioleoylphosphatidic acid (DOPA). The DOPA-covered Pt centers can be co-encapsulated in PLGA NPs alongside Sf to stimulate excellent anticancer property. The occurrence of the Pt centers suggestively enhanced the encapsulations of Sf into PLGA-NPs. Formation of the nanocomposite (Pt-Sf@PLGA-NPs) was confirmed by FTIR and X-ray spectroscopic techniques. Further, the morphology of Pt-Sf@PLGA-NPs and nanoparticle size was examined by scanning electron microscopic and transmission microscopy, respectively. Furthermore, Pt-Sf@PLGA-NPs induced significant apoptosis in human osteosarcoma MG-63 and U2OS cancer cells in vitro. The results suggest that Pt-Sf@PLGA-NPs are one of the promising human osteosarcoma cancer therapeutic candidates worthy of further investigations.