A hollow MnO2 nanoplatform for multimodal imaging and NIR-triggered ablation of endometriosis through mitochondrial apoptosis and fibrosis

• Targeted delivery to endometriosis lesions was achieved via the EPR effect. • This nanoplatform integrates multimodal imaging with NIR-triggered therapy. • Its mechanism induces mitochondrial apoptosis and TGF-β1/Smad upregulation. Endometriosis is a common gynecological condition that significantly reduces quality of life and fertility in affected women. Despite being histologically benign, it displays biological behaviors reminiscent of malignancy, such as invasive growth within pelvic organs and the peritoneum. This study investigates a platform utilizing hollow manganese dioxide nanoparticles (HMnO 2 @IR820 NPs) engineered to concurrently delineate and ablate endometriosis lesions. This is accomplished through the integration of multimodal imaging, near-infrared (NIR) light-triggered photothermal therapy (PTT), and photodynamic therapy (PDT). Following intravenous administration, HMnO 2 @IR820 NPs preferentially accumulate in endometriosis lesions due to the enhanced permeability and retention effect. These nanoparticles facilitate effective multimodal imaging and lesion ablation for endometriosis. HMnO 2 @IR820 NPs induce mitochondrial damage and trigger the caspase-dependent apoptotic pathway, leading to apoptosis in primary endometrial stromal cells. In parallel, treatment with these nanoparticles activates the TGF-β1/Smad signaling pathway, promoting collagen fiber deposition. Animal experiments conducted on New Zealand rabbits have further demonstrated that HMnO 2 @IR820 NPs exhibit targeted properties for various types of endometriosis lesions, enhancing the precision of diagnosis and synergistic PDT & PTT of the disease. In conclusion, HMnO 2 @IR820 NPs represent a promising multifunctional nanotheranostic platform, facilitating multimodal imaging and NIR light-induced ablation of endometriosis through mitochondrial apoptosis and profibrotic effects.