Chitosan-functionalised single-walled carbon nanotube-mediated drug delivery of SNX-2112 in cancer cells

J Biomater Appl. 2016 Sep;31(3):379-86. doi: 10.1177/0885328216651183. Epub 2016 May 26.

Abstract

Delivery of amphiphobic drugs (insoluble in both water and oil) has been a great challenge in drug delivery. SNX-2112, a novel inhibitor of Hsp90, is a promising drug candidate for treating various types of cancers; however, the insolubility greatly limits its clinical application. This study aimed to build a new type of drug delivery system using single-walled carbon nanotubes (SWNTs) for controllable release of SNX-2112; chitosan (CHI) was non-covalently added to SWNTs to improve their biocompatibility. SWNTs-CHI demonstrated high drug-loading capability; the release of SNX-2112 was pH triggered and time related. The intracellular reactive oxygen species of SWNTs-CHI increased, compared with that of SWNTs, leading to higher mitogen-activated protein kinase and cell apoptosis. The results of western-blotting, lactate dehydrogenase (LDH) release assay, and cell viability assay analyses indicated that apoptosis-related proteins were abundantly expressed in K562 cells and that the drug delivery system significantly inhibited K562 cells. Thus, SWNT-CHI/SNX-2112 shows great potential as a drug delivery system for cancer therapy.

Keywords: SNX-2112; Single-walled carbon nanotubes; cancer; chitosan; drug delivery; lactate dehydrogenase; reactive oxygen species.

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Apoptosis / drug effects
  • Chitosan / chemistry*
  • Delayed-Action Preparations / administration & dosage*
  • Delayed-Action Preparations / chemical synthesis
  • Diffusion
  • Heterocyclic Compounds, 4 or More Rings / administration & dosage*
  • Heterocyclic Compounds, 4 or More Rings / chemistry
  • Humans
  • K562 Cells
  • Nanocapsules / administration & dosage
  • Nanocapsules / chemistry*
  • Nanocapsules / ultrastructure
  • Nanotubes, Carbon / chemistry*
  • Nanotubes, Carbon / ultrastructure
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / pathology
  • Particle Size
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Delayed-Action Preparations
  • Heterocyclic Compounds, 4 or More Rings
  • Nanocapsules
  • Nanotubes, Carbon
  • SNX 2112
  • Chitosan