Melanin chelating zinc ions for NIR-I photoacoustic imaging-guided photothermal-pyroptosis therapy of breast cancer.

Melanin nanoparticles (MNPs), as an endogenous pigment, boasts excellent biocompatibility, multifunctional properties including photothermal conversion and radical scavenging, which exhibit broad potential for transformative biomedical applications. MNPs modified with polyethylene glycol-amine (PEG-NH2) exhibit superior near-infrared (NIR) absorption and stable photothermal performance. In this study, we designed and fabricated a melanin‑zinc ion chelation nanoplatform (MNP-Zn NPs). MNP-Zn NPs possessed ultrasmall size, PAI but also demonstrated high photothermal conversion efficiency under near infrared irradiation. Mechanistically, the system activated the Caspase 1/gasdermin D (GSDMD) pathway to trigger pyroptosis. This platform achieves highly efficient anti-tumor effects through the synergistic action of the photothermal effect of melanin and zinc ion-mediated pyroptosis. In vivo animal experiments demonstrated that MNP-Zn NPs possess excellent biocompatibility and can effectively induce tumor cell death under NIR excitation.