期刊
ACS CHEMICAL BIOLOGY
卷 17, 期 5, 页码 1082-1091出版社
AMER CHEMICAL SOC
DOI: 10.1021/acschembio.1c00925
关键词
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资金
- Government of Canada's New Frontiers in Research Fund (NFRF) [NFRFE-2020-00290]
- National Science Foundation [CHE 1653474]
- National Institutes of Health [NIGMS R15GM114792]
A newly discovered molecule capable of producing singlet oxygen in cells efficiently kills cancer cells and demonstrates cancer-selective action.
Reactive oxygen species (e.g., singlet oxygen) are the primary cytotoxic agents used in the clinically approved technique photodynamic therapy (PDT). Although singlet oxygen has high potential to effectively kill tumor cells, its production via light excitation of a photosensitizer has been limited by the penetration depth and delivery of light in tissue. To produce singlet oxygen without light excitation, we describe the use of Schaap's chemiluminescent scaffold comprising an adamantylidene-dioxetane motif. Functionalizing this scaffold with a photosensitizer, Erythrosin B, resulted in spontaneous chemiluminescence resonance energy transfer (CRET) leading to the production of singlet oxygen. We show that this compound is cell permeable and that the singlet oxygen produced via CRET is remarkably efficient in killing cancer cells at low micromolar concentrations. Moreover, we demonstrate that protection of the phenol on the chemiluminescent scaffold with a nitroreductase-responsive trigger group allows for cancer-selective dark dynamic cell death. Here, we present the concept of dark dynamic therapy using a small cell-permeable molecule capable of producing the effects of PDT in cells, without light
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