Generic Synthesis of Small-Sized Hollow Mesoporous Organosilica Nanoparticles for Oxygen-Independent X-ray-activated Synergistic Therapy

Nat Commun. 2019 Mar 18;10(1):1241. doi: 10.1038/s41467-019-09158-1.

Abstract

The success of radiotherapy relies on tumor-specific delivery of radiosensitizers to attenuate hypoxia resistance. Here we report an ammonia-assisted hot water etching strategy for the generic synthesis of a library of small-sized (sub-50 nm) hollow mesoporous organosilica nanoparticles (HMONs) with mono, double, triple, and even quadruple framework hybridization of diverse organic moieties by changing only the introduced bissilylated organosilica precursors. The biodegradable thioether-hybridized HMONs are chosen for efficient co-delivery of tert-butyl hydroperoxide (TBHP) and iron pentacarbonyl (Fe(CO)5). Distinct from conventional RT, radiodynamic therapy (RDT) is developed by taking advantage of X-ray-activated peroxy bond cleavage within TBHP to generate •OH, which can further attack Fe(CO)5 to release CO molecules for gas therapy. Detailed in vitro and in vivo studies reveal the X-ray-activated cascaded release of •OH and CO molecules from TBHP/Fe(CO)5 co-loaded PEGylated HMONs without reliance on oxygen, which brings about remarkable destructive effects against both normoxic and hypoxic cancers.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Carbon Monoxide / chemistry
  • Chemoradiotherapy / methods*
  • Drug Carriers / chemical synthesis*
  • Drug Liberation / radiation effects*
  • Female
  • Hep G2 Cells
  • Humans
  • Hydroxyl Radical / chemistry
  • Hydroxyl Radical / radiation effects
  • Iron Compounds / administration & dosage
  • Mice
  • Mice, Nude
  • Nanoparticles / chemistry
  • Neoplasms / therapy*
  • Organosilicon Compounds / chemical synthesis
  • Particle Size
  • Polyethylene Glycols / chemistry
  • Porosity
  • RAW 264.7 Cells
  • Treatment Outcome
  • X-Rays
  • Xenograft Model Antitumor Assays
  • tert-Butylhydroperoxide / administration & dosage
  • tert-Butylhydroperoxide / radiation effects

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Iron Compounds
  • Organosilicon Compounds
  • Hydroxyl Radical
  • Polyethylene Glycols
  • iron pentacarbonyl
  • Carbon Monoxide
  • tert-Butylhydroperoxide