A multifunctional graphene oxide-based nanoplatform sensitizes ovarian cancer to cisplatin via ROS-PINK1/Parkin mitophagy under chemo-photothermal-photodynamic synergy.

Ovarian cancer is the gynecological malignancy with the highest mortality rate. Platinum resistance remains a major clinical challenge, severely limiting the therapeutic efficacy of cisplatin-based chemotherapy. In recent years, nanomedicine delivery systems have emerged as a promising strategy to enhance the efficacy of conventional cancer treatments. Herein, we constructed a multifunctional graphene oxide-based nanoplatform by functionalizing graphene oxide with hyaluronic acid, gold nanorods, and indocyanine green, followed by loading of cisplatin to form GO-HA-GNRs-ICG@Pt. This nanoplatform exhibits remarkable photothermal and photodynamic conversion efficiency, active tumor-targeting capability, and pH/near-infrared light dual-responsive cisplatin release. More importantly, in vitro and in vivo studies demonstrate that GO-HA-GNRs-ICG@Pt achieves significantly higher therapeutic efficacy and better biosafety compared to cisplatin monotherapy in A2780 ovarian cancer cells. Mechanistically, we discovered that GO-HA-GNRs-ICG@Pt activates the ROS-PINK1/Parkin-mediated mitophagy signaling axis, ultimately enhancing the cisplatin sensitivity of ovarian cancer cells. This work not only provides a theoretical foundation for the development of targeted multifunctional nanoplatforms for integrated cancer therapy but also offers a new synergistic treatment strategy with potential for addressing drug resistance in clinical ovarian cancer.