Tumor-activated in situ synthesis of single-atom catalysts for O2-independent photodynamic therapy based on water-splitting

• Published in: Nature communications 2024-04, Vol.15 (1), p.2954-16, Article 2954
• Main Authors: Yin, Yiyan, Ge, Xiyang, Ouyang, Jin, Na, Na
• Format: Article
• Language: English
• Subjects: 140/58; 631/67/1059/602; 639/638/298/54/990; 639/638/77/884; Cancer; Cancer therapies; Carbon nitride; Catalysts; Cell death; Charge transfer; Chemical synthesis; Humanities and Social Sciences; Hydroxyl radicals; Hypoxia; Irradiation; Lipid peroxidation; Lipids; multidisciplinary; Peroxidation; Photodynamic therapy; Science; Science (multidisciplinary); Side effects; Single atom catalysts; Toxicity; Tumor microenvironment; Tumors; Water splitting
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-46987-1

Single-atom catalysts (SACs) have attracted interest in photodynamic therapy (PDT), while they are normally limited by the side effects on normal tissues and the interference from the Tumor Microenvironment (TME). Here we show a TME-activated in situ synthesis of SACs for efficient tumor-specific water-based PDT. Upon reduction by upregulated GSH in TME, C 3 N 4 -Mn SACs are obtained in TME with Mn atomically coordinated into the cavity of C 3 N 4 nanosheets. This in situ synthesis overcomes toxicity from random distribution and catalyst release in healthy tissues. Based on the Ligand-to-Metal charge transfer (LMCT) process, C 3 N 4 -Mn SACs exhibit enhanced absorption in the red-light region. Thereby, a water-splitting process is induced by C 3 N 4 -Mn SACs under 660 nm irradiation, which initiates the O 2 -independent generation of highly toxic hydroxyl radical (·OH) for cancer-specific PDT. Subsequently, the ·OH-initiated lipid peroxidation process is demonstrated to devote effective cancer cell death. The in situ synthesized SACs facilitate the precise cancer-specific conversion of inert H 2 O to reactive ·OH, which facilitates efficient cancer therapy in female mice. This strategy achieves efficient and precise cancer therapy, not only avoiding the side effects on normal tissues but also overcoming tumor hypoxia. The utility of single-atom catalysts (SACs) for photodynamic therapy (PDT) has been limited by tumor hypoxia and side effects on normal tissues. Here the authors address these issues by developing an approach of tumor microenvironment-activated in situ synthesis of SACs for tumor-specific water-based PDT.