Mechanism analysis of transgene expression induced by chitosan/hyaluronic acid nanoparticles in CD44v9/RHAMM co-expressed gastric cancer cells: contribution of hyaluronic acid to RHAMM-mediated intracellular transport

Glycoconj J. 2026 May 16;43(1):20. doi: 10.1007/s10719-026-10218-0.

Abstract

Optimizing non-viral vectors for gene therapy requires elucidating the molecular mechanisms underlying vector uptake and intracellular delivery. In this study, cell transfection using pDNA/polysaccharide complexes was investigated to develop a gene delivery system specific for gastric tumor cells that express hyaluronic acid (HA) receptors such as CD44 variant 9 (CD44v9) and receptor for hyaluronan-mediated motility (RHAMM). pDNA/chitosan/HA complexes showed specific transgene expression activity in CD44v9(+) cells, mediated by CD44v9-dependent cell uptake and microtubule-dependent transport. Particularly, RHAMM was involved in intracellular transport of pDNA/chitosan/HA complexes. We demonstrated that HA drives CD44v9-mediated internalization, RHAMM-mediated, and microtubule-dependent intracellular transport, which are essential for enhanced pDNA complex-driven gene expression in gastric cancer cells co-expressing CD44v9 and RHAMM.

Keywords: CD44v9; Chitosan; Gene delivery; Hyaluronic acid; RHAMM.

MeSH terms

  • Biological Transport
  • Cell Line, Tumor
  • Chitosan* / chemistry
  • Extracellular Matrix Proteins* / genetics
  • Extracellular Matrix Proteins* / metabolism
  • Gene Transfer Techniques
  • Humans
  • Hyaluronan Receptors* / genetics
  • Hyaluronan Receptors* / metabolism
  • Hyaluronic Acid* / chemistry
  • Hyaluronic Acid* / pharmacology
  • Nanoparticles* / chemistry
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / metabolism
  • Stomach Neoplasms* / pathology
  • Transfection
  • Transgenes*

Substances

  • Hyaluronan Receptors
  • Hyaluronic Acid
  • Chitosan
  • hyaluronan-mediated motility receptor
  • Extracellular Matrix Proteins
  • CD44 protein, human