Construction and antitumor evaluation of stimulus-responsive dual-drug micelles based on computer simulation

Abstract

The pathogenesis of cancer is highly complex, and a single anti-tumor drug is insufficient to fully suppress the tumor. Doxorubicin (DOX) is a commonly used antitumor drug; however, its severe cardiotoxicity, narrow therapeutic window, and the development of multidrug resistance (MDR) significantly limit its clinical application. To overcome the limitations of single chemotherapeutic agents and improve treatment outcomes, combination therapies involving different drugs are widely used in clinical practice. In this project, the compatibility of DOX and Curcumin (Cur), Paclitaxel (PTX) with Curcumol derivatives (CD-2e) was simulated by molecular dynamics, followed by dissipative particle dynamics (DPD) simulations to investigate the self-assembly process of drug-loaded micelles and the effect of the content of encapsulated drugs on the morphology and structure of the micelles. From these, Cur, a more compatible drug, was selected for co-delivery with DOX to the tumor site in GSH-stimulated responsive micelles to control drug release in the tumor tissue, thereby enhancing drug efficacy and reducing toxic side effects. This delivery system aimed to achieve controlled drug release within the tumor tissue, thereby enhancing drug efficacy and reducing toxic side effects. In vitro and in vivo experiments confirmed the stability and compatibility of the mPEG–SS–DOX/Cur micelles, demonstrating their potent antitumor effects and ability to mitigate drug-induced toxicity under redox conditions.