Dual-Targeted Pt@Ce-MOF Nanoplatform Enhances Radiotherapy Efficacy via Tumor-Specific Delivery and Mitochondrial...

The development of multifunctional nanoplatforms capable of enhancing the efficacy and precision of cancer radiochemotherapy remains a significant clinical need. Here, we report a dual-targeted cerium-based metal-organic framework nanoplatform (Pt@Ce-MOF-RGD/FA) designed for synergistic radiosensitization and chemotherapeutic delivery in breast cancer. The Ce-MOF core acts as a reactive oxygen species (ROS) amplifier under radiotherapy, while encapsulated cisplatin (Pt) serves as a chemotherapeutic agent. Surface modification with RGD and folic acid (FA) enables active targeting of tumor cells via αvβ3 integrin and folate receptor pathways. Comprehensive physicochemical characterization confirmed successful construction of the nanocomposite. In vitro, Pt@Ce-MOF-RGD/FA exhibited potent cytotoxicity, enhanced cellular uptake, inhibition of tumor cell migration, and robust ROS generation and mitochondrial membrane depolarization. In vivo fluorescence imaging demonstrated superior tumor accumulation of the dual-ligand-modified formulation. Under radiotherapy, Pt@Ce-MOF-RGD/FA achieved significant tumor growth suppression in a 4T1 murine breast cancer model without inducing systemic toxicity, as confirmed by blood biochemistry, hematological analysis, and histopathology. Collectively, this work presents a rationally engineered nanoplatform with precise tumor targeting, efficient drug delivery, and enhanced radiosensitization, offering a promising strategy for safe and effective cancer treatment.