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Abstract Photodynamic therapy (PDT) is currently limited by the inability of photosensitizers (PSs) to enter cancer cells and generate sufficient reactive oxygen species. Utilizing phosphorescent triplet states of novel PSs to generate singlet oxygen offers exciting possibilities for PDT. Here, we report phosphorescent octahedral molybdenum (Mo)‐based nanoclusters (NC) with tunable toxicity for PDT of cancer cells without use of rare or toxic elements. Upon irradiation with blue light, these molecules are excited to their singlet state and then undergo intersystem crossing to their triplet state. These NCs display surprising tunability between their cellular cytotoxicity and phototoxicity by modulating the apical halide ligand with a series of short chain fatty acids from trifluoroacetate to heptafluorobutyrate. The NCs are effective in PDT against breast, skin, pancreas, and colon cancer cells as well as their highly metastatic derivatives, demonstrating the robustness of these NCs in treating a wide variety of aggressive cancer cells. Furthermore, these NCs are internalized by cancer cells, remain in the lysosome, and can be modulated by the apical ligand to produce singlet oxygen. Thus, (Mo)‐based nanoclusters are an excellent platform for optimizing PSs. Our results highlight the profound impact of molecular nanocluster chemistry in PDT applications.
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Using Biological Photophysics to Map the Excited‐State Topology of Molecular Photosensitizers for Photodynamic Therapy
Abstract This study employs TLD1433, a RuII‐based photodynamic therapy (PDT) agent in human clinical trials, as a benchmark to establish protocols for studying the excited‐state dynamics of photosensitizers (PSs)in cellulo, in the local environment provided by human cancer cells. Very little is known about the excited‐state properties of any PS in live cells, and for TLD1433, it isterra incognita. This contribution targets a general problem in phototherapy, which is how to interrogate the light‐triggered, function‐determining processes of the PSs in the relevant biological environment, and establishes methodological advances to study the ultrafast photoinduced processes for TLD1433 when taken up by MCF7 cells. We generalize the methodological developments and results in terms of molecular physics by applying them to TLD1433’s analogue TLD1633, making this study a benchmark to investigate the excited‐state dynamics of phototoxic compounds in the complex biological environment.
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- Award ID(s):
- 2102459
- PAR ID:
- 10402555
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- Volume:
- 62
- Issue:
- 17
- ISSN:
- 1433-7851
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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