Manganese-Doped Metal-Organic Frameworks as a Multifunctional Agent for Targeted Diagnosis and Therapy in Nasopharyngeal Carcinoma

Despite improvements in survival rates for nasopharyngeal carcinoma (NPC) through optimized radiotherapy and chemotherapy, significant challenges persist, including difficulties in early detection of recurrence/metastasis and risks of collateral damage from radiosensitivity. In particular, during induction chemotherapy for NPC, drug targeting is crucial to enhance tumor-specific delivery, minimize systemic toxicities, and overcome resistance mechanisms, such as those driven by molecular pathways in EBV-associated cases. Developing multifunctional agents for targeted diagnosis and therapy is therefore critical. Herein, we report cRGD-Cy5.5@Mn-ZIF-8/5-FU, a powder material-based nanotheranostic platform demonstrating high efficacy for NPC. This multifunctional system integrates: 1) αvβ3 integrin-targeting cyclic RGD peptides for tumor-selective homing; 2) dual-modal imaging capabilities (Mn 2+ -dependent MRI contrast and Cy5.5-based near-infrared fluorescence); and 3) encapsulated 5-fluorouracil (5-FU) for chemotherapy. Preclinical evaluation reveals selective tumor accumulation and low systemic toxicity of cRGD-Cy5.5@Mn-ZIF-8/5-FU. The platform significantly suppresses NPC tumor progression compared to both free 5-FU and non-targeted Mn-ZIF-8/5-FU controls, confirming its targeted functionality. This integrated design enables real-time tumor visualization via fluorescence/MRI imaging concurrent with therapy. Our work offers a translatable powder material-based theranostic strategy for NPC, addressing challenges in therapeutic resistance and metastatic surveillance by unifying precise diagnosis and treatment within a single agent, while also establishing a nanoplatform foundation for combining diverse chemotherapeutic drugs in nasopharyngeal carcinoma therapy.