Metal-Free Far-Red Light-Driven Photolysis via Triplet Fusion to Enhance Checkpoint Blockade Immunotherapy

Angew Chem Int Ed Engl. 2023 Mar 6;62(11):e202218341. doi: 10.1002/anie.202218341. Epub 2023 Feb 1.

Abstract

Metal-free long-wavelength light-driven prodrug photoactivation is highly desirable for applications such as neuromodulation, drug delivery, and cancer therapy. Herein, via triplet fusion, we report on the far-red light-driven photo-release of an anti-cancer drug by coupling the boron-dipyrromethene (BODIPY)-based photosensitizer with a photocleavable perylene-based anti-cancer drug. Notably, this metal-free triplet fusion photolysis (TFP) strategy can be further advanced by incorporating an additional functional dopant, i.e. an immunotherapy medicine inhibiting the indoleamine 2,3-dioxygenase (IDO), with the far-red responsive triplet fusion pair in an air-stable nanoparticle. With this IDO inhibitor-assisted TFP system we observed efficient inhibition of primary and distant tumors in a mouse model at record-low excitation power, compared to other photo-assisted immunotherapy approaches. This metal-free TFP strategy will spur advancement in photonics and biophotonics fields.

Keywords: BODIPY; Photolysis; Triplet Fusion; Tumor Immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents*
  • Immune Checkpoint Inhibitors*
  • Immunotherapy
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Light
  • Mice
  • Photolysis

Substances

  • Immune Checkpoint Inhibitors
  • Antineoplastic Agents
  • Indoleamine-Pyrrole 2,3,-Dioxygenase