New Conjugates of Hyaluronic Acid with γ-Cyclodextrin as Sorafenib Carrier in Cancer Cells

ChemMedChem. 2024 Sep 16;19(18):e202400219. doi: 10.1002/cmdc.202400219. Epub 2024 Jul 17.

Abstract

In recent years, nanoparticles based on cyclodextrins have been widely investigated, mainly for drug delivery. In this work, we synthesized nanoparticles with a hyaluronic acid backbone (11 kDa and 45 kDa) functionalized with γ-cyclodextrins. We tested sorafenib in the presence of the new hyaluronan-cyclodextrin conjugates in A2780 (ovarian cancer), SK-HeP-1 (adenocarcinoma) and MDA-MB-453 (breast cancer) cell lines. We found that hyaluronan-cyclodextrin conjugates improve the antiproliferative activity of sorafenib. Remarkably, the system based on the 11 kDa hyaluronan conjugate was the most effective and, in the MDA-MB-453 cell line, significantly reduced the IC50 value of sorafenib cells by about 75 %.

Keywords: Cancer; Cyclodextrin; Drug delivery; Hyaluronic acid; Nanoparticles.

MeSH terms

  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation* / drug effects
  • Dose-Response Relationship, Drug
  • Drug Carriers* / chemical synthesis
  • Drug Carriers* / chemistry
  • Drug Screening Assays, Antitumor
  • Humans
  • Hyaluronic Acid* / chemical synthesis
  • Hyaluronic Acid* / chemistry
  • Hyaluronic Acid* / pharmacology
  • Molecular Structure
  • Nanoparticles / chemistry
  • Sorafenib* / chemistry
  • Sorafenib* / pharmacology
  • Structure-Activity Relationship
  • gamma-Cyclodextrins* / chemistry
  • gamma-Cyclodextrins* / pharmacology

Substances

  • Hyaluronic Acid
  • Sorafenib
  • gamma-Cyclodextrins
  • Antineoplastic Agents
  • Drug Carriers
  • gamma-cyclodextrin