Acid-sensitive ROS-triggered dextran-based drug delivery system for advanced chemo-photodynamic synergistic therapy

J Biomed Mater Res A. 2020 Jan;108(1):148-156. doi: 10.1002/jbm.a.36800. Epub 2019 Oct 11.

Abstract

In order to improve the treatment efficacy and reduce the side effects, the synergistic therapy has been effectively exploited in cancer treatment. Herein, we fabricated a kind of acid-sensitive ROS-triggered dextran-based drug delivery system (DHTD/Zn-TPP) for synergistic therapy, in which chemotherapeutics doxorubicin was conjugated to the dextran backbone via ROS cleavable thioketal conjugates while photosensitizer porphyrin (Zn-TPP) was encapsulated via acid-responsive metallic coordinated interaction. The structure and acid-responsive self-assemble behavior of DHTD/Zn-TPP were measured by 1 H NMR, Fourier transform infrared, dynamic laser scattering, and transmission electron microscopy. Further, the in vivo ROS-triggered DOX release and anticancer efficiency were evaluated toward HeLa cells and MCF-7 cells. All the data obtained verified that DHTD/Zn-TPP had a significantly improved cell growth inhibitory effect with light irritation due to the combined application of photodynamic-chemotherapy.

Keywords: acid sensitive; dextran; photodynamic-chemotherapy; reactive oxygen species sensitive; supramolecular metallic coordination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acids
  • Antineoplastic Agents / pharmacology*
  • Cell Death / drug effects
  • Dextrans / chemistry*
  • Drug Delivery Systems*
  • Drug Liberation
  • Drug Synergism
  • Endocytosis / drug effects
  • HeLa Cells
  • Humans
  • Hydrodynamics
  • MCF-7 Cells
  • Metalloporphyrins / chemical synthesis
  • Metalloporphyrins / chemistry
  • Micelles
  • Photochemotherapy*
  • Polymers / chemistry
  • Proton Magnetic Resonance Spectroscopy
  • Reactive Oxygen Species / metabolism*
  • Singlet Oxygen / analysis

Substances

  • Acids
  • Antineoplastic Agents
  • Dextrans
  • Metalloporphyrins
  • Micelles
  • Polymers
  • Reactive Oxygen Species
  • zinc tetraphenylporphine
  • Singlet Oxygen