Tumor selective uptake of drug-nanodiamond complexes improves therapeutic outcome in pancreatic cancer

Nanomedicine. 2019 Jun:18:112-121. doi: 10.1016/j.nano.2019.02.020. Epub 2019 Mar 6.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related deaths and novel treatment approaches are urgently needed. Here we show that poly(ethylene glycol)-functionalized nanodiamonds loaded with doxorubicin (ND-PEG-DOX) afforded a considerable improvement over free drug in an orthotopic pancreatic xenograft model. ND-PEG-DOX complexes were also superior to free DOX in 3-dimensional (3D) tumor spheroids of PDAC. ND-PEG showed no cytotoxicity towards macrophages, and histopathological analysis showed no abnormalities of major organs upon in vivo administration of ND-PEG-DOX. These results provide evidence that ND-mediated drug delivery may serve as a means of improving the therapeutic outcome in PDAC.

Keywords: Drug delivery; Nanodiamonds; Nanomedicine; Pancreatic adenocarcinoma.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use
  • Drug Liberation
  • Endocytosis / drug effects
  • Humans
  • Hydrodynamics
  • Male
  • Mice
  • Nanodiamonds / chemistry*
  • Nanodiamonds / ultrastructure
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / ultrastructure
  • Particle Size
  • Polyethylene Glycols / chemistry
  • Spheroids, Cellular / drug effects
  • Spheroids, Cellular / pathology
  • Tissue Distribution / drug effects
  • Treatment Outcome

Substances

  • Nanodiamonds
  • Polyethylene Glycols
  • Doxorubicin