A Thioacetal Photocage Designed for Dual Release: Application in the Quantitation of Therapeutic Release by Synchronous Reporter Decaging.
A Thioacetal Photocage Designed for Dual Release: Application in the Quantitation of Therapeutic Release by Synchronous Reporter Decaging.
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DOI：
10.1002/cbic.201600494
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发表时间：
2017-01-03
期刊：
影响因子：
3.2
通讯作者：
Choi, Seok Ki
中科院分区：
文献类型：
--
作者：
Wong, Pamela T.;Tang, Shengzhuang;Cannon, Jayme;Mukherjee, Jhindan;Isham, Danielle;Gam, Kristina;Payne, Michael;Yanik, Sean A.;Baker, James R., Jr.;Choi, Seok Ki
尽管有巨大的潜力，现有的光笼技术的应用是有限的，缺乏先进的笼工具。在这里，我们报告了一种新的硫缩醛邻硝基苯甲醛（TNB）双臂光笼的设计，使控制的同时释放两个有效载荷连接到一个单一的TNB单元。使用由商业6-硝基苯甲醛在一个步骤中制备的这种笼，合成了三种药物-荧光团缀合物，紫杉醇-TNB-姜黄素，紫杉醇-TNB-香豆素和阿霉素-TNB-香豆素，并且长波长UVA光触发释放实验证明，对于每种缀合物，发生双有效载荷释放，具有快速衰减动力学。在基于细胞的体外测定中，双重释放也可以通过UV暴露来控制，导致增加的细胞荧光和细胞毒性，与未修饰的药物对KB癌细胞系一样有效。这种双重释放的程度可通过原位测量的报告荧光来量化，并且发现与细胞毒性的程度相关。因此，这种新颖的双臂笼策略提供了一种有价值的工具，其能够在递送部位主动控制和实时监测药物活化。
Despite the immense potential, application of existing photocaging technology is limited by the paucity of advanced caging tools. Here we report on the design of a novel thioacetal ortho-nitrobenzaldehyde (TNB) dual arm photocage that enables control of the simultaneous release of two payloads linked to a single TNB unit. Using this cage which was prepared in a single step from commercial 6-nitroverataldehyde, three drug-fluorophore conjugates were synthesized, Taxol-TNB-Fluorescein, Taxol-TNB-Coumarin and Doxorubicin-TNB-Coumarin, and long wavelength UVA light-triggered release experiments demonstrated that dual payload release occurred with rapid decay kinetics for each conjugate. In cell based assays in vitro, dual release could also be controlled by UV exposure, resulting in increased cellular fluorescence and cytotoxicity as potent as unmodified drug towards the KB carcinoma cell line. The extent of such dual release was quantifiable by reporter fluorescence measured in situ, and found to correlate with the extent of cytotoxicity. Thus, this novel dual-arm cage strategy provides a valuable tool which enables both active control and real-time monitoring of drug activation at the delivery site.
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影响因子：
15
作者：
Agasti SS;Chompoosor A;You CC;Ghosh P;Kim CK;Rotello VM
通讯作者：
Rotello VM
DOI：
10.1039/c3cc42179a
发表时间：
2013-05-28
期刊：
Chemical communications (Cambridge, England)
影响因子：
--
作者：
Inlay MA;Choe V;Bharathi S;Fernhoff NB;Baker JR Jr;Weissman IL;Choi SK
通讯作者：
Choi SK
近红外光介导的阿霉素使用上转换纳米颗粒的释放。
DOI：
10.1039/c5cc01795e
发表时间：
2015-05-18
期刊：
Chemical communications (Cambridge, England)
影响因子：
--
作者：
Michael Dcona M;Yu Q;Capobianco JA;Hartman MC
通讯作者：
Hartman MC
影响因子：
4.6
作者：
Alansary D;Schmidt B;Dörr K;Bogeski I;Rieger H;Kless A;Niemeyer BA
通讯作者：
Niemeyer BA
影响因子：
3.5
作者：
Choi, Seok Ki;Verma, Manisha;Silpe, Justin;Moody, Ryan E.;Tang, Kenny;Hanson, Jeffrey J.;Baker, James R., Jr.
通讯作者：
Baker, James R., Jr.