Herein, we report an activatable near-infrared (NIR) afterglow theranostic prodrug that circumvents high background noise interference caused by external light excitation. The prodrug can release 10-hydroxycamptothecin (HCPT) and synchronously activate NIR afterglow luminescence in response to the high intratumoral peroxynitrite level associated with immunogenic cell death (ICD). The afterglow signal could monitor drug release, real-time visualize ICD progression and cold-to-hot tumor transformation. The prodrug itself is an ICD inducer achieved by photodynamic therapy (PDT). PDT initiates ICD and recruits first-arrived neutrophils to secrete peroxynitrite to trigger HCPT release. Intriguingly, we demonstrate that HCPT can significantly amplify PDT-mediated ICD process with a synergistic "0+1&gt;1" effect. The prodrug thus shows a self-sustainable ICD magnification effect by establishing an “ICD-HCPT release-amplified ICD” cycling loop. In vivo studies demonstrate that such a self-sustainable ICD magnifier delivers an excellent performance in completely eradicating existing tumor and preventing further tumor recurrence through enhanced antitumor immune response.

Activatable near-infrared afterglow theranostic prodrug with self-sustainable magnification effect of immunogenic cell death

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