Live-Fibroblast IR Imaging of a Cytoprotective PhotoCORM Activated with Visible Light

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• 作者：Fabio Zobi ; Luca Quaroni ; Giuseppe Santoro ; Theodora Zlateva ; Olivier Blacque ; Blagoj Sarafimov ; Marcus C. Schaub ; Anna Yu. Bogdanova
• 刊名：Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：September 12, 2013
• 年：2013
• 卷：56
• 期：17
• 页码：6719-6731
• 全文大小：690K
• 年卷期：v.56,no.17(September 12, 2013)
• ISSN：1520-4804

文摘

Carbon monoxide releasing molecules (CORMs) are an emerging class of pharmaceutical compounds currently evaluated in several preclinical disease models. There is general consensus that the therapeutic effects elicited by the molecules may be directly ascribed to the biological function of the released CO. It remains unclear, however, if cellular internalization of CORMs is a critical event in their therapeutic action. To address the problem of cellular delivery, we have devised a general strategy which entails conjugation of a CO-releasing molecule (here a photoactivated CORM) to the 5鈥?OH ribose group of vitamin B12. Cyanocobalamin (B₁₂) functions as the biocompatible water-soluble scaffold which actively transports the CORM against a concentration gradient into the cells. The uptake and cellular distribution of this B₁₂鈥損hotoCORM conjugate is demonstrated via synchrotron FTIR spectromicroscopy measurements on living cells. Intracellular photoinduced CO release prevents fibroblasts from dying under conditions of hypoxia and metabolic depletion, conditions that may occur in vivo during insufficient blood supply to oxygen-sensitive tissues such as the heart or brain.