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

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 mu...

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Bibliographic Details
Published in:Angewandte Chemie 2024-03, Vol.136 (11), p.n/a
Main Authors: Li, Zhikai, Zhang, Zhijun, Ma, Lingzhi, Wen, Haifei, Kang, Miaomiao, Li, Danxia, Zhang, Wenjing, Luo, Siqi, Wang, Weiguo, Zhang, Mingming, Wang, Dong, Li, Haiyang, Li, Xiaopeng, Wang, Heng
Format: Article
Language:English
Subjects:
Biocompatibility
Cage Compounds
Cancer therapies
Chromophores
Effectiveness
Functional groups
Metallography
Photodynamic Therapy
Photosensitizers
Porphyrins
Pyridinium
Reactive oxygen species
Self-Assembly
Supramolecular Chemistry
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Summary: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. Discrete metallo‐cages that combine multiple photosensitizer modules synergistically have been constructed through a simple method using pyrylium‐pyridinium salts and coordination‐driven self‐assembly. Compared with the modules, cages with a porphyrin core exhibit a significant enhancement in the generation of reactive oxygen species (ROS) and an enhanced efficacy in photodynamic therapy (PDT).
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.202400049