NIR light-controlled mitochondria-targeted delivery of carbon monoxide combined with histone deacetylase inhibition for synergistic anticancer therapy

J Inorg Biochem. 2022 Jan:226:111656. doi: 10.1016/j.jinorgbio.2021.111656. Epub 2021 Nov 9.

Abstract

A multifunctional nanoplatform APIPB-MnCO@TPP@N,P-GQDs (APIPB = N-(2-aminophen-yl)-4-(1H-imidazo[4,5-f] [1, 10] phenanthrolin-2-yl) benzamide, TPP = triphenylphosphine, Mn = manganese, CO = carbon monoxide, and GQDs = graphene quantum dots), nanoplatform (1), was synthesized, which consists of a fluorescent N, P-doped GQDs carrier with its surface covalently functionalized by an CO donor APIPB-MnCO with histone deacetylases (HDAC) inhibitory property and a TPP derivative directing group. Nanoplatform (1) selectively localized in the mitochondria of HeLa cells to inhibit HDAC activity, and released CO upon 808 nm near-infrared light irradiation, destroying the mitochondria and thus inducing cancer cells apoptosis. The targeted subcellular mitochondrial CO delivery combined with inhibitory HDAC activity maximized the cytotoxicity of the nanoplatform which may provide new insights for CO-mediated multimodal therapies for cancer treatment.

Keywords: Carbon monoxide; Graphene quantum dots nanoplatform; Histone deacetylase inhibitor; Light-controlled release; Manganese carbonyl complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Carbon Monoxide* / pharmacokinetics
  • Carbon Monoxide* / pharmacology
  • Drug Delivery Systems*
  • HeLa Cells
  • Histone Deacetylase Inhibitors* / pharmacokinetics
  • Histone Deacetylase Inhibitors* / pharmacology
  • Humans
  • Infrared Rays*
  • Mitochondria / metabolism*
  • Neoplasms* / drug therapy
  • Neoplasms* / metabolism
  • Phototherapy*

Substances

  • Histone Deacetylase Inhibitors
  • Carbon Monoxide