Melanin Nanoparticles Combined with CaO₂ Nanoparticles for Image-Guided Tumor Microenvironment-Responsive Multimodal Therapy

Nanomaterials that respond to specific tumor microenvironments (TMEs), such as weakly acidic, hypoxia, and high glutathione (GSH), have shown promise in killing cancer cells with low toxicity and high specificity. Herein, a multistimulus TME-responding nanoplatform, composed of MCMnH and CaO2 nanoparticles, was prepared based on the exploration of the new characteristics of melanin nanoparticles (MNPs), which was found to promote photosensitizers to produce reactive oxygen species (ROS) under NIR irradiation. The MCMnH + CaO2 nanoplatform showed excellent performance of alleviating tumor hypoxia and amplifying the ROS reaction through the dual channels of MnO2 and CaO2, thus improving the combined antitumor effect of chemodynamic therapy (CDT), photodynamic therapy (PDT), and photothermal therapy (PTT). Furthermore, the MCMnH + CaO2 nanoplatform also demonstrated the capability of multimethod imaging, such as magnetic resonance imaging (MRI) and fluorescence imaging, which provided multiple schemes for the monitoring of the tumor treatment process. In conclusion, safe and efficient treatment and monitoring were achieved through the versatile and green antitumor nanoplatform in this article. Our study shows a good demonstration of an image-guided tumor microenvironment-responsive nanoplatform in the multimodal strategy toward cancer therapy.