Nanomaterials for Endogenous and Exogenous Hydrogen Sulfide-Based NIR Photothermal Cancer Therapy: A Review

Hydrogen sulfide (H 2 S) is recognized as the third gaseous signaling molecule present, playing a crucial role in cellular processes. When designing nanomaterials, H 2 S not only serves as a cancer biomarker but also directly influences tumor cell proliferation and metastasis by modulating its concentration. However, gas donor inability to actively accumulate within tumors and release gas in a controlled manner results in restricted cancer treatment efficacy and potential toxic side effects. Near-infrared (NIR) responsive photothermal probes are characterized by their rapid response time, high selectivity, sensitivity, and noninvasive attributes. They offer the opportunity for precise, real-time, and controlled modulation of H 2 S concentrations at both cellular and murine levels. The integration of photothermal therapy with gas therapy and other treatment modalities through multifunctional nanocarrier platforms shows promise in enhancing cancer treatment outcomes while minimizing adverse effects. The development of multifunctional probes capable of controllably modulating H 2 S concentrations and photothermal properties is considered essential yet challenging in academic research. This Review critically assesses two primary approaches in tumor NIR photothermal strategies involving H 2 S: multifunctional photothermal probes targeted utilizing H 2 S as a biomarker and probes combining H 2 S gas therapy with photothermal and alternative modalities. Additionally, this Review addresses the current limitations of these technologies and outlines potential future directions for advancement. Overall, this Review aims to provide insights and guidance for the seamless integration of H 2 S and photothermal probes in cancer therapy, aligning with the rigorous standards of academic journals.