A Thioacetal Photocage Designed for Dual Release: Application in the Quantitation of Therapeutic Release by Synchronous Reporter Decaging

作者: Pamela T. Wong , Shengzhuang Tang , Jayme Cannon , Jhindan Mukherjee , Danielle Isham

DOI: 10.1002/CBIC.201600494

关键词:

摘要: Despite the immense potential, application of existing photocaging technology is limited by paucity advanced caging tools. Here we report on design a novel thioacetal ortho-nitrobenzaldehyde (TNB) dual arm photocage that enables control simultaneous release two payloads linked to single TNB unit. Using this cage which was prepared in step from commercial 6-nitroverataldehyde, three drug-fluorophore conjugates were synthesized, Taxol-TNB-Fluorescein, Taxol-TNB-Coumarin and Doxorubicin-TNB-Coumarin, long wavelength UVA light-triggered experiments demonstrated payload occurred with rapid decay kinetics for each conjugate. In cell based assays vitro, could also be controlled UV exposure, resulting increased cellular fluorescence cytotoxicity as potent unmodified drug towards KB carcinoma line. The extent such quantifiable reporter measured situ, found correlate cytotoxicity. Thus, dual-arm strategy provides valuable tool both active real-time monitoring activation at delivery site.

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