A Photosensitive Polymeric Carrier with a Renewable Singlet Oxygen Reservoir Regulated by Two NIR Beams for Enhanced Antitumor Phototherapy

Small. 2021 Jul;17(29):e2101180. doi: 10.1002/smll.202101180. Epub 2021 Jun 18.

Abstract

Photodynamic therapy (PDT), which utilizes photosensitizer to convert molecular oxygen into singlet oxygen (1 O2 ) upon laser irradiation to ablate tumors, will exacerbate the already oxygen shortage of most solid tumors and is thus self-limiting. Herein, a sophisticated photosensitive polymeric material (An-NP) that allows sustained 1 O2 generation and sufficient oxygen supply during the entire phototherapy is engineered by alternatively applying PDT and photothermal therapy (PTT) controlled by two NIR laser beams. In addition to a photosensitizer that generates 1 O2 , An-NP consists of two other key components: a molecularly designed anthracene derivative capable of trapping/releasing 1 O2 with superior reversibility and a dye J-aggregate with superb photothermal performance. Thus, in 655 nm laser-triggered PDT process, An-NP generates abundant 1 O2 with extra 1 O2 being trapped via the conversion into EPO-NP; while in the subsequent 785 nm laser-driven PTT process, the converted EPO-NP undergoes thermolysis to liberate the captured 1 O2 and regenerates An-NP. The intratumoral oxygen level can be replenished during the PTT cycle for the next round of PDT to generate 1 O2 . The working principle and phototherapy efficacy are preliminarily demonstrated in living cells and tumor-bearing mice, respectively.

Keywords: photoactive; photodynamic therapy; photothermal therapy; polymeric nanoparticles; singlet oxygen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Mice
  • Photochemotherapy*
  • Photosensitizing Agents / therapeutic use
  • Phototherapy
  • Singlet Oxygen*

Substances

  • Photosensitizing Agents
  • Singlet Oxygen