A trimodal magnetic navigation-enhanced nanoplatform for spatiotemporally controlled chemo-photodynamic synergistic cancer therapy

Abstract

Malignant tumors pose a serious threat to human health with their high incidence and mortality rates. Although chemotherapeutic agents such as doxorubicin (DOX) exhibit significant antitumor efficacy, their non-specific distribution leads to toxic side effects and mono-chemotherapy fails to achieve complete tumor eradication, significantly limiting clinical applications. This study presents the development and evaluation of a multifunctional nanoplatform, Fe₃O₄@Ce6-DOX@liposome, which integrates magnetic targeting, chemotherapy, and photodynamic therapy (PDT) for enhanced tumor treatment. The nanoparticles (NPs) were engineered to co-deliver the chemotherapeutic drug DOX and the photosensitizer chlorin e6 (Ce6), while superparamagnetic Fe₃O₄ enabled external magnetic guidance. In vitro studies in MCF-7 cells demonstrated the system's light-activated cytotoxicity, with confocal microscopy revealing precise spatiotemporal control over drug release and ROS generation. In vivo evaluation in 4T1 tumor-bearing mice showed that magnetic navigation significantly enhanced tumor accumulation of NPs, leading to 73% tumor growth inhibition through synergistic chemo-PDT effects. The combination of magnetic targeting and dual therapeutic modalities resulted in superior antitumor efficacy compared to individual treatments, with minimal systemic toxicity. These findings highlight the potential of this multifunctional nanoplatform as a precise and effective strategy for solid tumor therapy, offering improved targeting and reduced off-target effects compared to conventional treatments.