Near-infrared modulated photothermal/nanozymatic dual-modal strategy for combating cancer via molybdenum selenide nanourchins

Background: Breast cancer, a major health concern globally, often faces challenges in the non-invasive elimination of cancer cells. This has prompted researchers to explore alternative strategies, such as photothermal therapy (PTT), which takes advantage of the location of breast cancer lesions. Additionally, the tumor microenvironment with high hydrogen peroxide (H2O2) provides a key prerequisite for treating tumors with nanozymes, especially those with peroxidase (POD)-like activity. However, the overexpression ofTrxR1, which maintains redox homeostasis in tumor cells, limits reactive oxygen species (ROS)-based cytotoxic therapy. This study aims to present molybdenum selenide nano urchins (MoSe2 NUs) with excellent photothermal conversion efficiency, POD-like activity and selective inhibition ofTrxR1 to achieve photothermal enhanced nanocatalytic therapy for combating breast cancer. Methods: The characterization of MoSe2 NUs synthesized by the hydrothermal method was identified byTEM, XRD, Zeta potential and DLS. Whether MoSe2 NUs in conjunction with NIR possessed POD-like activities or not was identified via a TMB colorimetric method. The photothermal characteristics of MoSe2 NUs excited by near- infrared were recorded by an infrared thermal imaging camera.The antitumor effect of MoSe2 NUs was detected by cell death staining, apoptosis assay and animal experiments.TrxR1 and apoptosis-related protein expression were identified by Western blot and Immunohistochemistry. Results: MoSe2 NUs possessed excellent photothermal conversion efficiency, peroxidase (POD)-like activity, and selective inhibition ofTrxR1. Furthermore, the photo- thermal effect of MoSe2 NUs can enhance their POD-like activity, allowing for accurate cancer treatment under near-infrared (NIR) light. MoSe2 NUs plus NIR and MoSe2 NUs alone exhibited in vivo tumor inhibition rates of 69.7% and 35.1%, respectively. Mechanistically, NIR-regulated MoSe2 NUs induced potent apoptosis of cancer cells by downregulating the TrxR1 and elevating intracellular ROS, thereby leading to caspase-3 cleavage. Conclusions: This study demonstrated that MoSe2 NUs under NIR irradiation can precisely and efficiently treat breast cancer and have great potential for clinical application.