In Vitro Cellular Uptake and Dimerization of Signal Transducer and Activator of Transcription-3 (STAT3) Identify the Photosensitizing and Imaging-Potential of Isomeric Photosensitizers Derived from Ch

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• 作者：Avinash Srivatsan ; Yanfang Wang ; Penny Joshi ; Munawwar Sajjad ; Yihui Chen ; Chao Liu ; Krishnakumar Thankppan ; Joseph R. Missert ; Erin Tracy ; Janet Morgan ; Nestor Rigual ; Heinz Baumann ; Ravindra K. Pandey
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：October 13, 2011
• 年：2011
• 卷：54
• 期：19
• 页码：6859-6873
• 全文大小：1521K
• 年卷期：v.54,no.19(October 13, 2011)
• ISSN：1520-4804

文摘

Among the photosensitizers investigated, both ring-D and ring-B reduced chlorins containing the m-iodobenzyloxyethyl group at position-3 and a carboxylic acid functionality at position-17² showed the highest uptake by tumor cells and light-dependent photoreaction that correlated with maximal tumor-imaging [positron emission tomography (PET) and fluorescence] and long-term photodynamic therapy (PDT) efficacy in BALB/c mice bearing Colon26 tumors. However, among the ring-D reduced compounds, the isomer containing the 1鈥?m-iobenzyloxyethyl group at position-3 was more effective than the corresponding 8-(1鈥?i>-m-iodobenzyloxyethyl) derivative. All photosensitizers showed maximum uptake by tumor tissue 24 h after injection, and the tumors exposed with light at low fluence and fluence rates (128 J/cm², 14 mW/cm²) produced significantly enhanced tumor eradication than those exposed at higher fluence and fluence rate (135 J/cm², 75 mW/cm²). Interestingly, dose-dependent cellular uptake of the compounds and light-dependent STAT3 dimerization have emerged as sensitive rapid indicators for PDT efficacy in vitro and in vivo and could be used as in vitro/in vivo biomarkers for evaluating and optimizing the in vivo treatment parameters of the existing and new PDT candidates.