Combination of starvation therapy and Pt-NP based chemotherapy for synergistic cancer treatment

Abstract

Platinum nanoparticles (Pt-NPs) have been developed for enhanced toxicity against tumor cells. However, the therapeutic effect of Pt-NPs was severely limited by the lack of cellular uptake of Pt-NPs and an oxidative environment. The combination of starvation therapy with Pt-NP based chemotherapy in a well-designed nano-system is expected to eliminate tumors. Therefore, GOx and Pt-NPs were coated with PLGA to obtain a functional nano-system (GOx–Pt-NS), which increased the cellular uptake of Pt-NPs. The accumulation of GOx–Pt-NS in tumors increased significantly via the enhanced permeability and retention (EPR) effect of nanoparticles. In addition, protection of the GOx–Pt-NS overcame several drawbacks of GOx such as poor stability, short in vivo half-life, immunogenicity, and systemic toxicity. Glucose oxidase (GOx) elevated the gluconic acid ROS levels in tumor cells, resulting in an acidic and oxidative environment. The acidic and oxidative environment enhanced the conversion of Pt²⁺via Pt NPs as well as DNA-binding ability. Finally, combining GOx based starvation therapy with Pt-NP based chemotherapy was expected to eliminate tumors more efficiently through a synergistic strategy.