Enhanced targeted treatment of cervical cancer using nanoparticle-based doxycycline delivery system

Sci Rep. 2025 Jan 17;15(1):2318. doi: 10.1038/s41598-024-84203-8.

Abstract

This study investigates a nanoparticle-based doxycycline (DOX) delivery system targeting cervical cancer cells via the CD44 receptor. Molecular docking revealed a strong binding affinity between hyaluronic acid (HA) and CD44 (binding energy: -7.2 kJ/mol). Characterization of the HA-Chitosan nanoparticles showed a particle size of 284.6 nm, a zeta potential of 16.9 mV, and a polydispersity index of 0.314, with SEM confirming smooth surface morphology. The encapsulation efficiency of DOX-loaded nanoparticles was 89.32%, exhibiting a sustained release profile, with 67.45% released over 72 h in acidic conditions (pH 5.5). Cytotoxicity assays demonstrated a significant reduction in HeLa cell viability to 22% at 72 h, compared to 67% in normal HEK cells. Stability tests confirmed the maintenance of nanoparticle integrity and a consistent drug release profile over three months. Cell migration was reduced by 45%, and RT-PCR analysis revealed a 53% downregulation of TNF-α expression, suggesting effective targeting of inflammatory pathways. These results underscore the potential of HA-Chitosan-based DOX nanoparticles in improving cervical cancer treatment through enhanced targeted delivery and inhibition of tumor-promoting mechanisms.

Keywords: Cervical Cancer; Doxycycline; Immunotherapy; Novel Drug Delivery System; Sustained release; Targeted therapy.

MeSH terms

  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Chitosan* / chemistry
  • Doxycycline* / administration & dosage
  • Doxycycline* / chemistry
  • Doxycycline* / pharmacology
  • Drug Carriers / chemistry
  • Drug Delivery Systems
  • Drug Liberation
  • Female
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Hyaluronan Receptors / metabolism
  • Hyaluronic Acid* / chemistry
  • Molecular Docking Simulation
  • Nanoparticle Drug Delivery System / chemistry
  • Nanoparticles* / chemistry
  • Particle Size
  • Uterine Cervical Neoplasms* / drug therapy
  • Uterine Cervical Neoplasms* / metabolism
  • Uterine Cervical Neoplasms* / pathology

Substances

  • Doxycycline
  • Chitosan
  • Hyaluronic Acid
  • Hyaluronan Receptors
  • Drug Carriers
  • Nanoparticle Drug Delivery System