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 in facing 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@CaCO₃^Aptamer/ICG, was designed for the competent synergistic photothermal therapy (PTT) and photodynamic therapy (PDT) under the guidance of photothermal (PT) and magnetic resonance (MR) imaging. The nanoplatform's aptamer modification targeting the transferrin receptor (TfR) and the epithelial cell adhesion molecule (EpCAM) on breast cancer cells, and the acid degradable CaCO₃ shell allowed for effective tumor accumulation and TME‐responsive payload release in situ. The nanoplatform also exhibited excellent PDT properties due to its ability to generate O₂ and consume antioxidant GSH in tumors. Additionally, the synergistic therapy was achieved by a single wavelength of near‐infrared (NIR) laser. RNA sequencing was performed to identify differentially expressed genes (DEGs), which showed that the expressions of proliferation and migration‐associated genes were inhibited, while the apoptosis and immune response gene expressions were upregulated after the synergistic treatments. This multifunctional nanoplatform that responds to the TME to realize the on‐demand payload release and enhancs PDT induced by TME modulation holds great promise for clinical applications in tumor therapy.

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