| Autor: |
Digby EM; Department of Chemical and Physical Sciences, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, Ontario L5L 1C6, Canada., Tung MT; Department of Chemical and Physical Sciences, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, Ontario L5L 1C6, Canada., Kagalwala HN; Department of Chemistry, Center for Drug Discovery, Design, and Delivery (CD4), and Center for Global Health Impact (CGHI), Southern Methodist University, Dallas, Texas 75205-0314, United States., Ryan LS; Department of Chemistry, Center for Drug Discovery, Design, and Delivery (CD4), and Center for Global Health Impact (CGHI), Southern Methodist University, Dallas, Texas 75205-0314, United States., Lippert AR; Department of Chemistry, Center for Drug Discovery, Design, and Delivery (CD4), and Center for Global Health Impact (CGHI), Southern Methodist University, Dallas, Texas 75205-0314, United States., Beharry AA; Department of Chemical and Physical Sciences, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, Ontario L5L 1C6, Canada. |
| Abstrakt: |
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. |
