Self-immolative poly(thiocarbamate) with localized H2S signal amplification for precise cancer imaging and therapy
Qingyu Zong, Jun Li, Qing Xu, Ye Liu, Kewei Wang, Youyong Yuan
Abstract
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 (SNPp-Cy) or nanomedicine (SNPp-DOX) for cancer imaging and therapy, respectively. SNPp-Cy exhibits a low detection limit for hydrogen sulfide, enabling ultrasensitive detection of small (<2 mm) tumors in female mice. In addition, SNPp-DOX can effectively inhibit the growth of DOX-resistant human breast cancer xenograft, lung metastasis, and patient-derived xenograft tumors in female mice. Hydrogen sulfide is essential in many biological processes and a promising cancer imaging and signalling molecule and therapeutic agent, but the potential applications are hindered by its low endogenous levels. Here, the authors develop a nanoplatform based on H2S-responsive self-immolative poly(thiocarbamate) with localized H2S signal amplification capability and use the nanoplatform to encapsulate an H2S-responsive fluorescent probe or an anticancer prodrug.