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

<jats:title>Abstract</jats:title><jats:p>Hydrogen sulfide (H<jats:sub>2</jats:sub>S) as an important biological gasotransmitter plays a pivotal role in many physiological and pathological processes. The sensitive and quantitative detection of H<jats:sub>2</jats:sub>S 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, H<jats:sub>2</jats:sub>S-responsive and depleting nanoplatform (ZNNPs) for quantitative and real-time imaging of endogenous H<jats:sub>2</jats:sub>S for early diagnosis and treatment of H<jats:sub>2</jats:sub>S-associated diseases. We show that ZNNPs exhibit unexpected NIR conversion (F<jats:sub>1070 </jats:sub>→ F<jats:sub>720</jats:sub>) and ratiometric photoacoustic (PA<jats:sub>680</jats:sub>/PA<jats:sub>900</jats:sub>) signal responsiveness towards H<jats:sub>2</jats:sub>S, allowing for sensitive and quantitative visualization of H<jats:sub>2</jats:sub>S in acute hepatotoxicity, cerebral hemorrhage model as well as colorectal tumors in living mice. ZNNPs@FA simultaneously scavenges the mitochondrial H<jats:sub>2</jats:sub>S 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 H<jats:sub>2</jats:sub>S in related diseases.</jats:p>