Enhancing Photodynamic Therapy through Resonance Energy Transfer Constructed Near-Infrared Photosensitized Nanoparticles

Adv Mater. 2017 Jul;29(28):10.1002/adma.201604789. doi: 10.1002/adma.201604789. Epub 2017 Jun 6.

Abstract

Photodynamic therapy (PDT) is an important cancer treatment modality due to its minimally invasive nature. However, the efficiency of existing PDT drug molecules in the deep-tissue-penetrable near-infrared (NIR) region has been the major hurdle that has hindered further development and clinical usage of PDT. Thus, herein a strategy is presented to utilize a resonance energy transfer (RET) mechanism to construct a novel dyad photosensitizer which is able to dramatically boost NIR photon utility and enhance singlet oxygen generation. In this work, the energy donor moiety (distyryl-BODIPY) is connected to a photosensitizer (i.e., diiodo-distyryl-BODIPY) to form a dyad molecule (RET-BDP). The resulting RET-BDP shows significantly enhanced absorption and singlet oxygen efficiency relative to that of the acceptor moiety of the photosensitizer alone in the NIR range. After being encapsulated with biodegradable copolymer pluronic F-127-folic acid (F-127-FA), RET-BDP molecules can form uniform and small organic nanoparticles that are water soluble and tumor targetable. Used in conjunction with an exceptionally low-power NIR LED light irradiation (10 mW cm-2 ), these nanoparticles show superior tumor-targeted therapeutic PDT effects against cancer cells both in vitro and in vivo relative to unmodified photosensitizers. This study offers a new method to expand the options for designing NIR-absorbing photosensitizers for future clinical cancer treatments.

Keywords: bodipy; nanoparticles; near-infrared radiation; photodynamic therapy; resonance energy transfer.

MeSH terms

  • Animals
  • Boron Compounds / chemistry
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Energy Transfer
  • Folic Acid / chemistry
  • Humans
  • Infrared Rays*
  • Mice
  • Micelles
  • Microscopy, Confocal
  • Nanoparticles / chemistry*
  • Neoplasms / diagnostic imaging
  • Neoplasms / drug therapy
  • Photochemotherapy
  • Photosensitizing Agents / chemistry*
  • Photosensitizing Agents / pharmacology
  • Photosensitizing Agents / therapeutic use
  • Poloxamer / chemistry
  • Polymers / chemistry
  • Transplantation, Heterologous

Substances

  • 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
  • Boron Compounds
  • Micelles
  • Photosensitizing Agents
  • Polymers
  • Poloxamer
  • Folic Acid