Glycodendron/pyropheophorbide-a (Ppa)-functionalized hyaluronic acid as a nanosystem for tumor photodynamic therapy

Carbohydr Polym. 2020 Nov 1:247:116749. doi: 10.1016/j.carbpol.2020.116749. Epub 2020 Jul 12.

Abstract

To enhance the drug delivery efficiency of hyaluronic acid (HA), we designed and prepared glycodendron and pyropheophorbide-a (Ppa)-functionalized HA (HA-Ppa-Dendron) as a nanosystem for cancer photodynamic therapy. Linear Ppa-modified HA (HA-Ppa) was also prepared as a control. Cellular uptake of both polymers by MDA-MB-231 cells led to mitochondrial dysfunction and generation of reactive oxygen species under the irradiation of a laser. Compared to the linear polymer, HA-Ppa-Dendron had higher molecular weight, a more compact nanoscale particle size, and a dendritic structure, resulting in a much longer blood circulation time and higher tumor accumulation. HA-Ppa-Dendron outperformed HA-Ppa in inhibiting cell growth, with 60 % of tumors was eradicated under laser irradiation. Tumor growth inhibition (TGI) up to 99.2 % was achieved from HA-Ppa-Dendron, which was much higher than that of HA-Ppa (50.6 %). Therefore, glycodendron-functionalized HAs by integration of HA and dendritic polymers may act as efficient anti-cancer nanomedicine.

Keywords: Dendrimer; Drug delivery; Hyaluronic acid; Nanomedicines; Photodynamic therapy.

MeSH terms

  • Animals
  • Anthracenes / chemistry*
  • Apoptosis
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Proliferation
  • Chlorophyll / analogs & derivatives*
  • Chlorophyll / chemistry
  • Female
  • Humans
  • Hyaluronic Acid / chemistry*
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Photochemotherapy*
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Anthracenes
  • Photosensitizing Agents
  • dendron
  • Chlorophyll
  • pyropheophorbide a
  • Hyaluronic Acid