A homologous cell membrane-camouflaged iridium-doped carbon dot nanozyme for multimodal imaging-guided radiosensitization.

Abstract

Radiotherapy (RT) is a mainstay of cancer treatment, yet its efficacy is limited by tumor hypoxia, elevated glutathione (GSH) levels, and a lack of tumor-specific radiosensitizers. Herein, we synthesized iridium-doped carbon dots (Ir-CDs) and further camouflaged them with 4T1 cancer cell membranes to construct a biomimetic nanoplatform (Ir-CDs@CM) integrating homologous targeting, multimodal imaging, and nanozyme-mediated properties for enhanced radiosensitization. The synthesized Ir-CDs exhibited a uniform size of ∼2.25 nm and good water dispersibility. After encapsulation with 4T1 cell membranes, Ir-CDs@CM showed an average hydrodynamic diameter of ∼181.9 nm and a zeta potential of -17.0 mV, along with excellent colloidal stability, low cytotoxicity, favorable biocompatibility, and homologous targeting capability. Functionally, Ir-CDs@CM enabled dual-mode fluorescence (FL) and computed tomography (CT) imaging. Moreover, Ir-CDs displayed three nanozyme activities: GSH-depletion activity (47.13% GSH depletion), catalase-like activity (O2 generation up to 11.9 mg L-1), and peroxidase-like activity (a 5.17-fold increase in reactive oxygen species (ROS) generation under X-ray irradiation). This nanozyme-mediated oxygen evolution and ROS generation reduced 4T1 cell viability from 83% to 45.69% under 6 Gy irradiation. In vivo, the nanoplatform achieved excellent tumor accumulation and therapeutic efficacy in subcutaneous tumor-bearing mice, suppressing tumor growth within 14 days. Body weight fluctuations remained below 5% with no hepatorenal toxicity or tissue damage, confirming excellent biosafety. This strategy integrates membrane camouflage with iridium-based nanozyme technology for targeted imaging, microenvironment modulation, and radiosensitization, opening new avenues for integrated tumor therapy and diagnosis.