Enhanced photodynamic therapy based on an amphiphilic branched copolymer with pendant vinyl groups for simultaneous GSH depletion and Ce6 release

J Mater Chem B. 2020 Jan 22;8(3):478-483. doi: 10.1039/c9tb02120e.

Abstract

Photodynamic therapy would suffer from low efficiency in the cancer treatment process if the reactive oxygen species (ROS) generated from a photosensitizer (PS) were reduced by intracellular glutathione (GSH). To overcome this limitation, in this work, we developed an amphiphilic branched copolymer with pendant vinyl groups, and it self-assembled with chlorin e6 (Ce6) into nanoparticles to fabricate a GSH-reaction response drug delivery system. The vinyl groups in the hydrophobic core of the nanoparticles were reacted with GSH by a "thio-ene" click reaction to release Ce6; simultaneously, the level of GSH decreased for enhanced PDT. Both in vitro and in vivo studies demonstrated that remarkable PDT efficacy for the nanosystem can be achieved.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Chlorophyllides
  • Drug Screening Assays, Antitumor
  • Glutathione / antagonists & inhibitors*
  • Glutathione / metabolism
  • Humans
  • Materials Testing
  • Mice
  • Neoplasms, Experimental / diagnostic imaging
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / metabolism
  • Particle Size
  • Photochemotherapy*
  • Photosensitizing Agents / chemical synthesis
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology*
  • Polymers / chemical synthesis
  • Polymers / chemistry
  • Polymers / pharmacology
  • Porphyrins / metabolism*
  • Reactive Oxygen Species / metabolism
  • Surface Properties
  • Surface-Active Agents / chemical synthesis
  • Surface-Active Agents / chemistry
  • Surface-Active Agents / pharmacology*
  • Vinyl Compounds / chemistry
  • Vinyl Compounds / pharmacology

Substances

  • Antineoplastic Agents
  • Chlorophyllides
  • Photosensitizing Agents
  • Polymers
  • Porphyrins
  • Reactive Oxygen Species
  • Surface-Active Agents
  • Vinyl Compounds
  • phytochlorin
  • Glutathione