Computer Simulation on Polymer Micelles Combined Administration of Gambogic Acid and Curcumin as a Novel Anti-Cancer Drug Carrier

Purpose: The poor efficacy of traditional antitumor drugs in the treatment of cancer is mainly due to poor water solubility, systemic cytotoxicity, poor tumor targeting and other factors. In recent years, the nano-drug system has been widely studied in tumor therapy and drug targeting, but the design process requires repeated experiments, which are time consuming and laborious. In this context, we developed a novel synergistic co-delivery nanomicelle of gambogic acid and curcumin through molecular dynamics (MD) and dissipative particle dynamics (DPD) simulation. Methods: The synergistic effect was verified by the comprehensive index, apoptosis, reactive oxygen species (ROS) detection, and apoptosis-related protein experiments. MD and DPD simulations were utilized to design micelles. According to the results, methoxypolyethylene glycol (mPEG)-gambogic acid (GA)-curcumin (CU) micelles were synthesized and prepared for the co-delivery of GA and curcumin, and then, the micelles were characterized and released in vitro. Finally, a cytotoxicity study of micelles was carried out to prove its anti-tumor effect. Results: It was verified that the combined administration of GA and curcumin showed a synergistic effect in tumor cells (HepG2) and an antagonistic or weak synergistic effect in normal cells (BV2, HEK293). According to the design of computer simulation, mPEG-GA-CU micelles were synthesized and characterized. Cytotoxicity experiments proved that mPEG-GA-CU micelles are more toxic to HepG2 cells than BV2, HEK293 cells. Conclusions: Studies have shown that the mPEG-GA-CU nanomicelles designed by computer simulation have the ability to co-deliver drugs, play a synergistic anti-tumor effect, and have great potential in further anti-cancer practical applications.