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

Nat Commun. 2024 Aug 30;15(1):7558. doi: 10.1038/s41467-024-52006-0.

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.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Breast Neoplasms / diagnostic imaging
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Doxorubicin* / administration & dosage
  • Doxorubicin* / pharmacology
  • Doxorubicin* / therapeutic use
  • Female
  • Fluorescent Dyes / chemistry
  • Humans
  • Hydrogen Sulfide* / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticles / chemistry
  • Neoplasms / diagnostic imaging
  • Neoplasms / drug therapy
  • Optical Imaging / methods
  • Prodrugs / chemistry
  • Prodrugs / pharmacology
  • Prodrugs / therapeutic use
  • Xenograft Model Antitumor Assays

Substances

  • Hydrogen Sulfide
  • Doxorubicin
  • Fluorescent Dyes
  • Prodrugs
  • Antineoplastic Agents