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A Thioacetal Photocage Designed for Dual Release: Application in the Quantitation of Therapeutic Release by Synchronous Reporter Decaging.
Wong, Pamela T; Tang, Shengzhuang; Cannon, Jayme; Mukherjee, Jhindan; Isham, Danielle; Gam, Kristina; Payne, Michael; Yanik, Sean A; Baker, James R; Choi, Seok Ki.
Afiliação
  • Wong PT; Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, 1150 W. Medical Ctr. Drive, Ann Arbor, MI, 48109, USA.
  • Tang S; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
  • Cannon J; Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, 1150 W. Medical Ctr. Drive, Ann Arbor, MI, 48109, USA.
  • Mukherjee J; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
  • Isham D; Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, 1150 W. Medical Ctr. Drive, Ann Arbor, MI, 48109, USA.
  • Gam K; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
  • Payne M; Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, 1150 W. Medical Ctr. Drive, Ann Arbor, MI, 48109, USA.
  • Yanik SA; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
  • Baker JR; Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, 1150 W. Medical Ctr. Drive, Ann Arbor, MI, 48109, USA.
  • Choi SK; Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, 1150 W. Medical Ctr. Drive, Ann Arbor, MI, 48109, USA.
Chembiochem ; 18(1): 126-135, 2017 Jan 03.
Article em En | MEDLINE | ID: mdl-27902870
ABSTRACT
Despite the immense potential of existing photocaging technology, its application 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 enabled control of the simultaneous release of two payloads linked to a single TNB unit. By 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 performed in vitro, dual release could also be controlled by UV exposure, resulting in increased cellular fluorescence and cytotoxicity with potency equal to that of unmodified drug towards the KB carcinoma cell line. The extent of such dual release was quantifiable by reporter fluorescence measured in situ and was found to correlate with the extent of cytotoxicity. Thus, this novel dual arm cage strategy provides a valuable tool that enables both active control and real-time monitoring of drug activation at the delivery site.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Benzaldeídos / Portadores de Fármacos Limite: Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Benzaldeídos / Portadores de Fármacos Limite: Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article