A hydrogen sulphide-responsive and depleting nanoplatform for cancer photodynamic therapy

Hydrogen sulfide (H₂S) as an important biological gasotransmitter plays a pivotal role in many physiological and pathological processes. The sensitive and quantitative detection of H₂S level is therefore crucial for precise diagnosis and prognosis evaluation of various diseases but remains a huge challenge due to the lack of accurate and reliable analytical methods in vivo. In this work, we report a smart, H₂S-responsive and depleting nanoplatform (ZNNPs) for quantitative and real-time imaging of endogenous H₂S for early diagnosis and treatment of H₂S-associated diseases. We show that ZNNPs exhibit unexpected NIR conversion (F₁₀₇₀→ F₇₂₀) and ratiometric photoacoustic (PA₆₈₀/PA₉₀₀) signal responsiveness towards H₂S, allowing for sensitive and quantitative visualization of H₂S in acute hepatotoxicity, cerebral hemorrhage model as well as colorectal tumors in living mice. ZNNPs@FA simultaneously scavenges the mitochondrial H₂S in tumors leading to significant ATP reduction and severe mitochondrial damage, together with the activated photodynamic effect, resulting in efficient suppression of colorectal tumor growth in mice. We believe that this platform may provide a powerful tool for studying the vital impacts of H₂S in related diseases.