Mn2+/Ir3+‐Doped and CaCO3‐Covered Prussian Blue Nanoparticles with Indocyanine Green Encapsulation for Tumor Microenvironment Modulation and Image‐Guided Synergistic Cancer Therapy

Abstract The development of smart theranostic nanoplatforms has gained great interest in effective cancer treatment against the complex tumor microenvironment (TME), including weak acidity, hypoxia, and glutathione (GSH) overexpression. Herein, a TME‐responsive nanoplatform named PMIC Apt /ICG, based on PB:Mn&Ir@CaCO 3 Aptamer /ICG, is designed for the competent synergistic photothermal therapy and photodynamic therapy (PDT) under the guidance of photothermal and magnetic resonance imaging. The nanoplatform's aptamer modification targeting the transferrin receptor and the epithelial cell adhesion molecule on breast cancer cells, and the acid degradable CaCO 3 shell allow for effective tumor accumulation and TME‐responsive payload release in situ. The nanoplatform also exhibits excellent PDT properties due to its ability to generate O 2 and consume antioxidant GSH in tumors. Additionally, the synergistic therapy is achieved by a single wavelength of near‐infrared laser. RNA sequencing is performed to identify differentially expressed genes, which show that the expressions of proliferation and migration‐associated genes are inhibited, while the apoptosis and immune response gene expressions are upregulated after the synergistic treatments. This multifunctional nanoplatform that responds to the TME to realize the on‐demand payload release and enhance PDT induced by TME modulation holds great promise for clinical applications in tumor therapy.