Combining Multiple Photosensitizer Modules into One Supramolecular System for Synergetic Enhanced Photodynamic Therapy

Angew Chem Int Ed Engl. 2024 Mar 11;63(11):e202400049. doi: 10.1002/anie.202400049. Epub 2024 Jan 23.

Abstract

Photodynamic therapy (PDT), as an emerging cancer treatment, requires the development of highly desirable photosensitizers (PSs) with integrated functional groups to achieve enhanced therapeutic efficacy. Coordination-driven self-assembly (CDSA) would provide an alternative approach for combining multiple PSs synergistically. Here, we demonstrate a simple yet powerful strategy of combining conventional chromophores (tetraphenylethylene, porphyrin, or Zn-porphyrin) with pyridinium salt PSs together through condensation reactions, followed by CDSA to construct a series of novel metallo-supramolecular PSs (S1-S3). The generation of reactive oxygen species (ROS) is dramatically enhanced by the direct combination of two different PSs, and further reinforced in the subsequent ensembles. Among all the ensembles, S2 with two porphyrin cores shows the highest ROS generation efficiency, specific interactions with lysosome, and strong emission for probing cells. Moreover, the cellular and living experiments confirm that S2 has excellent PDT efficacy, biocompatibility, and biosafety. As such, this study will enable the development of more efficient PSs with potential clinical applications.

Keywords: Cage Compounds; Photodynamic Therapy; Photosensitizers; Self-Assembly; Supramolecular Chemistry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Neoplasms* / drug therapy
  • Photochemotherapy*
  • Photosensitizing Agents / therapeutic use
  • Porphyrins* / pharmacology
  • Porphyrins* / therapeutic use
  • Reactive Oxygen Species

Substances

  • Photosensitizing Agents
  • Reactive Oxygen Species
  • Porphyrins