Toward Precise Antitumoral Photodynamic Therapy Using a Dual Receptor-Mediated Bioorthogonal Activation Approach |
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Authors: | Dr Jacky C H Chu Dr Clarence T T Wong Prof Dennis K P Ng |
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Institution: | Department of Chemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China |
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Abstract: | Targeted delivery and specific activation of photosensitizers can greatly improve the treatment outcome of photodynamic therapy. To this end, we report herein a novel dual receptor-mediated bioorthogonal activation approach to enhance the tumor specificity of the photodynamic action. It involves the targeted delivery of a biotinylated boron dipyrromethene (BODIPY)-based photosensitizer, which is quenched in the native form by the attached 1,2,4,5-tetrazine unit, and an epidermal growth factor receptor (EGFR)-targeting cyclic peptide conjugated with a bicycle6.1.0]non-4-yne moiety. Only for cancer cells that overexpress both the biotin receptor and EGFR, the two components can be internalized preferentially where they undergo an inverse electron-demand Diels–Alder reaction, leading to restoration of the photodynamic activity of the BODIPY core. By using a range of cell lines with different expression levels of these two receptors, we have demonstrated that this stepwise “deliver-and-click” approach can confine the photodynamic action on a specific type of cancer cells. |
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Keywords: | Bioorthogonal Chemistry Boron Dipyrromethene Dual Receptor Inverse Electron-Demand Diels–Alder Reaction Photodynamic Therapy |
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