Self-immolative poly(thiocarbamate) with localized H₂S signal amplification for precise cancer imaging and therapy

Hydrogen sulfide is essential in numerous physiological and pathological processes and has emerged as a promising cancer imaging and signaling molecule and a potentially versatile therapeutic agent. However, the endogenous levels of hydrogen sulfide remain insufficient to perform its biological functions, and thus, developing novel strategies that amplify hydrogen sulfide signals at lesion sites is of increasing interest. In this work, a nanoplatform (SNP) based on hydrogen sulfide-responsive self-immolative poly(thiocarbamate) with localized hydrogen sulfide signal amplification capability is developed to encapsulate a hydrogen sulfide-responsive fluorescent probe (e.g., hemicyanine dye; p-Cy) or an anticancer prodrug (e.g., doxorubicin; p-DOX) to form a nanoprobe (SNP_p-Cy) or nanomedicine (SNP_p-DOX) for cancer imaging and therapy, respectively. SNP_p-Cy exhibits a low detection limit for hydrogen sulfide, enabling ultrasensitive detection of small (<2 mm) tumors in female mice. In addition, SNP_p-DOX can effectively inhibit the growth of DOX-resistant human breast cancer xenograft, lung metastasis, and patient-derived xenograft tumors in female mice.