Ternary-Responsive Drug Delivery with Activatable Dual Mode Contrast-Enhanced in Vivo Imaging

ACS Appl Mater Interfaces. 2018 Sep 26;10(38):31947-31958. doi: 10.1021/acsami.8b10564. Epub 2018 Sep 13.

Abstract

Designing a smart nanotheranostic system has recently attracted tremendous attention and is highly desirable for realizing targeted cancer therapy and early diagnosis. Herein we report the fabrication of smart nanotheranostic system using multiresponsive gatekeeping protocol of mesoporous silica nanoparticles (MSN). Acid, oxidative stress and redox sensitive manganese oxide (MnO x) coated superparamagnetic iron oxide nanoparticle (SPION) were employed as nanolids to regulate the camptothecin drug release from the channels of mesoporous silica and achieve responsive dual-mode MRI contrast. The nonvehicle showed high magnetization and T2 contrast in magnetic resonance imaging (MRI) due to the significant density of SPION onto the surface of MSN, and at the same time the MnO x shell degradation release Mn2+ which enhanced the T1MRI visualization. The efficacy of responsive drug delivery system was investigated on pancreatic cancer cells and tumor-bearing mice, and results reinforced that MnO x-SPION@MSN@CPT nonvehicle is efficacious against cancer cells. We envision that our unique and multiresponsive nanoplatform may find applications in effective delivering of imaging and therapeutic agents to wide range of diseases besides cancer.

Keywords: MRI; drug delivery; manganese oxide; mesoporous silica; multiresponsive.

MeSH terms

  • Animals
  • Camptothecin / metabolism
  • Cell Line, Tumor
  • Contrast Media
  • Drug Delivery Systems / methods*
  • Ferric Compounds / chemistry
  • Humans
  • Magnetic Resonance Imaging*
  • Manganese Compounds / chemistry
  • Mice
  • Nanoparticles / chemistry*
  • Oxides / chemistry
  • Silicon Dioxide / chemistry

Substances

  • Contrast Media
  • Ferric Compounds
  • Manganese Compounds
  • Oxides
  • ferric oxide
  • manganese oxide
  • Silicon Dioxide
  • Camptothecin