Covalent Organic Framework-Supported Molecularly Dispersed Near-Infrared Dyes Boost Immunogenic Phototherapy against Tumors

Photodynamic therapy (PDT) mediated by near-infrared (NIR) dyes is a promising cancer treatment modality; however, its use is limited by significant challenges, such as hypoxic tumor microenvironments and self-quenching of photosensitizers. These challenges hamper its utility in inducing immunogenic cell death (ICD) and triggering potent systemic antitumor immune responses. This study demonstrates that molecular dispersion of NIR dyes in nanocarriers can significantly enhance their ability to produce reactive oxygen species and potentiate synergistic PDT and photothermal therapy against tumors. Specifically, NIR dye indocyanine green (ICG) can be spontaneously adsorbed to covalent organic frameworks (COFs) via pi-pi conjugations to prevent intermolecular stacking interactions. Then, ICG-loaded COFs are ultrasonically exfoliated and coated with polydopamine (PDA) to construct a new phototherapeutic agent ICG@COF-1@PDA with enhanced efficacy. In conjunction with ICG@COF-1@PDA, a single round of NIR laser irradiation can induce obvious ICD, elicit antitumor immunity in colorectal cancer, and yield 62.9% inhibition of untreated distant tumors. ICG@COF-1@PDA also exhibits notable phototherapeutic efficacy against 4T1 murine breast to lung metastasis, a spontaneous metastasis mode for triple-negative breast cancers (TNBCs). Overall, this study reveals a novel nanodelivery system for molecular dispersion of NIR dyes, which may present new therapeutic opportunities against primary and metastatic tumors.