Mesoporous silica nanoparticles loaded with fluorescent coumarin-5-fluorouracil conjugates as mitochondrial-targeting theranostic probes for tumor cells

Nanotechnology. 2021 Aug 19;32(45). doi: 10.1088/1361-6528/ac19d6.

Abstract

In this study, a nanodrug carrier (mesoporous silica nanoparticle (MSN)-SS-cysteamine hydrochloride (CS)-hyaluronic acid (HA)) for targeted drug delivery was prepared using MSNs, in which HA was used as a targeting ligand and blocking agent to control drug release. Coumarin is a fluorescent molecule that targets mitochondria. Two conjugates (XDS-DJ and 5-FUA-4C-XDS) were synthesized by chemically coupling nitrogen mustard and 5-fluorouracil with coumarin, which was further loaded into MSN-SS-CS-HA nanocarriers. MTT analysis demonstrated that the nanocomposite MSN-SS-CS@5-FUA-4C-XDS/HA displayed stronger cytotoxicity toward HCT-116 cells than HeLa or QSG-7701 cells. Furthermore, MSN-SS-CS@5-FUA-4C-XDS/HA was able to target the mitochondria of HCT-116 cells, causing decreased mitochondrial membrane potential and excessive production of reactive oxygen species. These results indicate that MSN-SS-CS@5-FUA-4C-XDS/HA has the potential to be a nanodrug delivery system for the treatment of colon cancer.

Keywords: drug delivery system; hyaluronic acid; imaging; mesoporous silica; mitochondria apoptosis.

MeSH terms

  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Coumarins / chemical synthesis*
  • Coumarins / chemistry
  • Coumarins / pharmacology
  • Cysteamine / chemistry*
  • Drug Compounding
  • Fluorouracil / chemistry*
  • HCT116 Cells
  • HeLa Cells
  • Humans
  • Hyaluronic Acid / chemistry*
  • Mechlorethamine / chemistry
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Nanoparticles
  • Particle Size
  • Porosity
  • Reactive Oxygen Species / metabolism
  • Silicon Dioxide
  • Theranostic Nanomedicine

Substances

  • Coumarins
  • Reactive Oxygen Species
  • Mechlorethamine
  • Cysteamine
  • Silicon Dioxide
  • Hyaluronic Acid
  • Fluorouracil