Self-Amplified Photodynamic Therapy through the 1 O2 -Mediated Internalization of Photosensitizers from a Ppa-Bearing Block Copolymer

Angew Chem Int Ed Engl. 2020 Feb 24;59(9):3711-3717. doi: 10.1002/anie.201914434. Epub 2020 Jan 30.

Abstract

Nanocarriers are employed to deliver photosensitizers for photodynamic therapy (PDT) through the enhanced penetration and retention effect, but disadvantages including the premature leakage and non-selective release of photosensitizers still exist. Herein, we report a 1 O2 -responsive block copolymer (POEGMA-b-P(MAA-co-VSPpaMA) to enhance PDT via the controllable release of photosensitizers. Once nanoparticles formed by the block copolymer have accumulated in a tumor and have been taken up by cancer cells, pyropheophorbide a (Ppa) could be controllably released by singlet oxygen (1 O2 ) generated by light irradiation, enhancing the photosensitization. This was demonstrated by confocal laser scanning microscopy and in vivo fluorescence imaging. The 1 O2 -responsiveness of POEGMA-b-P(MAA-co-VSPpaMA) block copolymer enabled the realization of self-amplified photodynamic therapy by the regulation of Ppa release using NIR illumination. This may provide a new insight into the design of precise PDT.

Keywords: block copolymer; drug delivery; photodynamic therapy; reactive oxygen species; self-amplification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chlorophyll / analogs & derivatives*
  • Chlorophyll / chemistry
  • Chlorophyll / metabolism
  • Chlorophyll / pharmacology
  • Chlorophyll / therapeutic use
  • Infrared Rays
  • Melanoma, Experimental / diagnostic imaging
  • Melanoma, Experimental / drug therapy
  • Mice
  • Microscopy, Confocal
  • Nanoparticles / chemistry*
  • Particle Size
  • Photochemotherapy
  • Photosensitizing Agents / chemistry*
  • Photosensitizing Agents / metabolism
  • Photosensitizing Agents / pharmacology
  • Photosensitizing Agents / therapeutic use
  • Polyethylene Glycols / chemistry
  • Polymers / chemistry*
  • Porphyrins / chemistry
  • Porphyrins / pharmacology
  • Positron-Emission Tomography
  • Singlet Oxygen / metabolism*

Substances

  • POEGMA
  • Photosensitizing Agents
  • Polymers
  • Porphyrins
  • Chlorophyll
  • Singlet Oxygen
  • pyropheophorbide a
  • Polyethylene Glycols