Biomimetic Diselenide-Bridged Mesoporous Organosilica Nanoparticles as an X-ray-Responsive Biodegradable Carrier for Chemo-Immunotherapy

Adv Mater. 2020 Dec;32(50):e2004385. doi: 10.1002/adma.202004385. Epub 2020 Nov 9.

Abstract

Chemotherapy causes off-target toxicity and is often ineffective against solid tumors. Targeted and on-demand release of chemotherapeutics remains a challenge. Here, cancer-cell-membrane-coated mesoporous organosilica nanoparticles (MONs) containing X-ray- and reactive oxygen species (ROS)-responsive diselenide bonds for controlled release of doxorubicin (DOX) at tumor sites are developed. DOX-loaded MONs coated with 4T1 breast cancer cell membranes (CM@MON@DOX) show greater accumulation at tumor sites and prolonged blood circulation time versus an uncoated control in mice bearing 4T1 orthotopic mammary tumors. Under low-dose X-ray radiation, the DOX-loaded MONs exhibit carrier degradation-controlled release via cleavage of diselenide bonds, resulting in DOX-mediated immunogenic cell death at the tumor site. Combination with a PD-L1 checkpoint blockade further enhances inhibition of tumor growth and metastasis with low systemic toxicity. Together, the findings show the promise of these biomimetic, radiation-responsive diselenide-bond-bridged MONs in chemo-immunotherapy.

Keywords: X-ray radiation responsivity; biodegradable mesoporous organosilica nanoparticles; biomimetic; chemo-immunotherapy; diselenide bonds.

MeSH terms

  • Animals
  • Biomimetic Materials* / chemistry
  • Biomimetic Materials* / pharmacology
  • Cell Line, Tumor
  • Doxorubicin* / chemistry
  • Doxorubicin* / pharmacology
  • Doxorubicin* / therapeutic use
  • Drug Carriers* / chemistry
  • Drug Liberation
  • Female
  • Humans
  • Immunotherapy*
  • Mice
  • Nanoparticles* / chemistry
  • Organoselenium Compounds / chemistry
  • Organoselenium Compounds / pharmacology
  • Organosilicon Compounds / chemistry
  • Organosilicon Compounds / pharmacology
  • Porosity
  • Reactive Oxygen Species / metabolism
  • X-Rays

Substances

  • Doxorubicin
  • Drug Carriers
  • Reactive Oxygen Species
  • Organosilicon Compounds
  • Organoselenium Compounds