A Versatile Carbon Monoxide Nanogenerator for Enhanced Tumor Therapy and Anti-Inflammation

ACS Nano. 2019 May 28;13(5):5523-5532. doi: 10.1021/acsnano.9b00345. Epub 2019 May 6.

Abstract

Carbon monoxide (CO) is regarded as a potential therapeutic agent with multiple beneficial functions for biomedical applications. In this study, a versatile CO nanogenerator (designated as PPOSD) was fabricated and developed for tumor therapy and anti-inflammation. Partially oxidized tin disulfide (SnS2) nanosheets (POS NSs) were decorated with a tumor-targeting polymer (polyethylene glycol-cyclo(Asp-d-Phe-Lys-Arg-Gly), PEG-cRGD), followed by the loading of chemotherapeutic drug doxorubicin (DOX) to prepare polymer@POS@DOX, or PPOSD. After injected intravenously, PPOSD could selectively accumulate in tumor tissue via the cRGD-mediated tumor recognition. Upon 561 nm laser irradiation, the POS moiety in PPOSD can photoreduce CO2 to CO, which significantly sensitized the chemotherapeutic effect of DOX. The POS in PPOSD can also act as a photothermal agent for effective photothermal therapy (PTT) of the tumor upon 808 nm laser irradiation. Furthermore, the generated CO can simultaneously decrease the inflammatory reaction caused by PTT. Blood analysis and hematoxylin-eosin staining of major organs showed that no obvious systemic toxicity was induced after the treatment, suggesting good biosafety of PPOSD. This versatile CO nanogenerator will find great potential for both enhanced tumor inhibition and anti-inflammation.

Keywords: anti-inflammation; carbon monoxide; photothermal therapy; sensitization; tumor inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Carbon Dioxide / chemistry
  • Carbon Monoxide / chemistry
  • Carbon Monoxide / pharmacology*
  • Cell Line, Tumor
  • Disulfides / chemistry
  • Disulfides / pharmacology
  • Doxorubicin / pharmacology
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • Mice
  • Nanoparticles / chemistry
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Xenograft Model Antitumor Assays

Substances

  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Disulfides
  • Carbon Dioxide
  • Carbon Monoxide
  • Doxorubicin