Chitosan coated pH-responsive metal-polyphenol delivery platform for melanoma chemotherapy

Carbohydr Polym. 2021 Jul 15:264:118000. doi: 10.1016/j.carbpol.2021.118000. Epub 2021 Mar 27.

Abstract

The safe and effective drug delivery system is important for cancer therapy. Here in, we first constructed a delivery system Cabazitaxel(Cab)@MPN/CS between metal-polyphenol (MPN) and chitosan (CS) to deliver Cab for melanoma therapy. The preparation process is simple, green, and controllable. After introducing CS coating, the drug loading was improved from 7.56 % to 9.28 %. Cab@MPN/CS NPs released Cab continuously under acid tumor microenvironment. The zeta potential of Cab@MPN/CS NPs could be controlled by changing the ratio of Cab@MPN and CS solutions. The positively charged Cab@MPN/CS accelerate B16F10 cell internalization. After internalized, Cab@MPN/CS NPs could escape from lysosomes via the proton sponge effect. The permeability of CS promotes the penetration of Cab@MPN/CS to the deeper B16F10 tumor spheroids. In vivo results showed that Cab@MPN/CS NPs have a longer retention time in tumor tissues and significantly inhibit tumor growth by up-regulating TUNEL expression and down-regulating KI67 and CD31 expression. Thus, this delivery system provides a promising strategy for the tumor therapy in clinic.

Keywords: Chemotherapy; Chitosan; Melanoma; Metal-polyphenol; pH-responsiveness.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Chitosan / chemistry*
  • Drug Carriers / chemistry
  • Drug Delivery Systems / methods*
  • Drug Liberation
  • Hydrogen-Ion Concentration
  • Ki-67 Antigen / metabolism
  • Melanoma / drug therapy*
  • Melanoma / metabolism
  • Metal Nanoparticles / chemistry*
  • Mice
  • Particle Size
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Polyphenols / chemistry*
  • Taxoids / chemistry
  • Taxoids / pharmacology*
  • Tumor Microenvironment / drug effects

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Ki-67 Antigen
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Polyphenols
  • Taxoids
  • cabazitaxel
  • Chitosan