Dacarbazine-primed carbon quantum dots coated with breast cancer cell-derived exosomes for improved breast cancer therapy

J Control Release. 2024 Jan:365:43-59. doi: 10.1016/j.jconrel.2023.11.005. Epub 2023 Nov 19.

Abstract

Imprecise targeting of chemotherapeutic drugs often leads to severe toxicity during breast cancer therapy. To address this issue, we have devised a strategy to load dacarbazine (DC) into fucose-based carbon quantum dots (CQDs), which are subsequently coated with exosomes (Ex-DC@CQDs) derived from breast cancer cells. Nanoparticle tracking analysis and western blotting revealed that Ex-DC@CQDs retained the structural and functional characteristics of exosomes. We found that exosomes facilitated the transport of DC@CQDs to cancer cells via heparan sulfate proteoglycan (HSPG) receptors, followed by an augmented depolarization of the mitochondrial membrane potential, ROS generation, and induction of apoptosis leading to cell death. In vivo imaging and pharmacokinetic studies demonstrated enhanced antitumor targeting and efficacy compared to free DC which we attribute to an improved pharmacokinetic profile, a greater tumor accumulation via exosome-mediated- HSPG receptor-driven cell uptake, and sustained release of the Ex-DC@CQDs. Our findings may pave the way for the further development of biologically sourced nanocarriers for breast cancer targeting.

Keywords: Breast cancer; Carbon quantum dots; Exosomes; HSPG receptor; Therapeutic targeting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / metabolism
  • Carbon / chemistry
  • Dacarbazine
  • Exosomes* / metabolism
  • Female
  • Heparan Sulfate Proteoglycans / metabolism
  • Humans
  • Quantum Dots* / chemistry

Substances

  • Dacarbazine
  • Heparan Sulfate Proteoglycans
  • Carbon