Auranofin-Loaded Chitosan Nanoparticles Demonstrate Potency against Triple-Negative Breast Cancer

Maame Abena O. Afrifa, Jong H. Kim, Kathryn A. Pitton, Chibuzor Olelewe, Adedamola S. Arojojoye, Douglas R. Strachan, Mark A. Suckow, Samuel G. Awuah

Research output: Contribution to journalArticlepeer-review

Abstract

Triple-negative breast cancer (TNBC) remains a clinical challenge due to molecular, metabolic, and genetic heterogeneity as well as the lack of validated drug targets. Thus, therapies or delivery paradigms are needed. Gold-derived compounds including the FDA-approved drug, auranofin have shown promise as effective anticancer agents against several tumors. To improve the solubility and bioavailability of auranofin, we hypothesized that the nanodelivery of auranofin using biodegradable chitosan modified polyethylene glycol (PEG) nanoparticles (NPs) will enhance anticancer activity against TNBC by comparing the best nanoformulation with the free drug. The selection of the nanoformulation was based on synthesis of various chitosan PEG copolymers via formaldehyde-mediated engraftment of PEG onto chitosan to form [chitosan-g-PEG] copolymer. Furthermore, altered physiochemical properties of the copolymer was based on the formaldehyde ratio towards nanoparticles (CP 1-4 NPs). Following the recruitment of PEG onto the chitosan polymer surface, we explored how this process influenced the stiffness of the nanoparticle using atomic force microscopy (AFM), a factor crucial for in vitro and in vivo studies. Our objective was to ensure the full functionality and inherent properties of chitosan as the parent polymer was maintained without allowing PEG to overshadow chitosan’s unique cationic properties while improving solubility in neutral pH. Hence, CP 2 NP was chosen. To demonstrate the efficacy of CP 2 NP as a good delivery carrier for auranofin, we administered a dose of 3 mg/kg of auranofin, in contrast to free auranofin, which was given at 5 mg/kg. In vivo studies revealed the potency of encapsulated auranofin against TNBC cells with a severe necrotic effect following treatment superior to that of free auranofin. In conclusion, chitosan-g-PEG nanoparticles have the potential to be an excellent delivery system for auranofin, increasing its effectiveness and potentially reducing its clinical limitations.

Original languageEnglish
Pages (from-to)2012-2022
Number of pages11
JournalACS Applied Bio Materials
Volume7
Issue number3
DOIs
StatePublished - Mar 18 2024

Bibliographical note

Publisher Copyright:
© 2024 American Chemical Society

Keywords

  • PEG
  • atomic force microscopy (AFM)
  • auranofin
  • chitosan
  • nanoparticle
  • triple-negative breast cancer (TNBC)

ASJC Scopus subject areas

  • Biomaterials
  • General Chemistry
  • Biomedical Engineering
  • Biochemistry, medical

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