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Significance Clinical applications of Pt(II)-based anticancer agents have been hampered because of drug resistance, severe side effects, and lack of precise guidance for the therapeutic procedure. To address these issues, we use molecular-dye–modified melanin dots as a multifunctional drug delivery platform to effectively deliver a Pt(II) metallacycle to tumor sites via an enhanced permeability and retention effect. In vivo studies show that nano-agent 1 displays strong NIR-II fluorescence and photoacoustic signals from tumors with a high signal-to-background ratio and successfully guides chemo-photothermal therapy with a superior antitumor performance and reduced side effects. These promising results will provide an opportunity for the design of novel multimodal and synergistic therapeutic agents for biomedical applications.

Melanin-dot–mediated delivery of metallacycle for NIR-II/photoacoustic dual-modal imaging-guided chemo-photothermal synergistic therapy