A novel pH-sensitive targeting polysaccharide-gold nanorod conjugate for combined photothermal-chemotherapy of breast cancer

Carbohydr Polym. 2019 May 15:212:334-344. doi: 10.1016/j.carbpol.2019.02.045. Epub 2019 Feb 19.

Abstract

Chemo-photothermal combination therapy is a promising strategy for cancer treatment. In this study, to achieve the combined photothermal-chemotherapy of breast cancer, a pH-sensitive oxidized hyaluronic acid-decorated dihydroxyphenyl/hydrazide bifunctionalized hydroxyethyl chitosan (DHHC)-gold nanorod (GNR) conjugate was developed. DHHC was synthesized by successive dihydroxyphenylation and hydrazidation of hydroxyethyl chitosan through carbodiimide reaction and click chemistry, respectively. The conjugate was obtained by chemically bonding DHHC onto GNR via Au-catechol bonds. Doxorubicin (DOX) was loaded onto the conjugate via an acid-labile hydrazone linkage with a drug loading content of 5.1%. DOX-loaded conjugate displayed good stability in neutral aqueous solutions and exhibited pH-responsive drug release and surface charge reversal behaviors. In vitro biological studies indicated that the conjugate could be effectively internalized by breast cancer MCF-7 cells and synergistic therapeutic effects were demonstrated, suggesting its great potential in combined photothermal-chemotherapy of breast cancer.

Keywords: Breast cancer; Combined photothermal-chemotherapy; Gold nanorod; Hydroxyethyl chitosan.

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Dose-Response Relationship, Drug
  • Doxorubicin / administration & dosage
  • Doxorubicin / chemistry*
  • Drug Delivery Systems / methods
  • Female
  • Gold / administration & dosage
  • Gold / chemistry*
  • Humans
  • Hydrogen-Ion Concentration
  • MCF-7 Cells
  • Nanotubes / chemistry*
  • Phototherapy / methods*
  • Polysaccharides / administration & dosage
  • Polysaccharides / chemistry*

Substances

  • Antineoplastic Agents
  • Polysaccharides
  • Gold
  • Doxorubicin