Photolitec, LLC , 73 High Street , Buffalo , New York 14226 , United States.
Institute of Basic and Applied Sciences , Egypt-Japan University of Science and Technology , Qesm Borg Al Arab 21934 , Egypt.
J Med Chem. 2019 Mar 14;62(5):2598-2617. doi: 10.1021/acs.jmedchem.8b01927. Epub 2019 Mar 5.
The in vitro and in vivo anticancer activity of iodinated photosensitizers (PSs) with and without an erlotinib moiety was investigated in UMUC3 [epidermal growth factor (EGFR)-positive] and T24 (EGFR-low) cell lines and tumored mice. Both the erlotinib-conjugated PSs 3 and 5 showed EGFR target specificity, but the position-3 erlotinib-PS conjugate 3 demonstrated lower photodynamic therapy efficacy than the corresponding non-erlotinib analogue 1, whereas the conjugate 5 containing an erlotinib moiety at position-17 of the PS showed higher tumor uptake and long-term tumor cure (severe combined immunodeficient mice bearing UMUC3 tumors). PS-erlotinib conjugates in the absence of light were ineffective in vitro and in vivo, but robust apoptotic and necrotic cell death was observed in bladder cancer cells after exposing them to a laser light at 665 nm. In contrast to F-fluorodeoxyglucose, a positron emission tomography agent, the position-17 erlotinib conjugate (I-analogue 6) showed enhanced UMUC3 tumor contrast even at a low imaging dose of 15 μCi/mouse.
研究了带有和不带有厄洛替尼部分的碘代光敏剂（PSs）的体外和体内抗癌活性，这些 PSs 用于 UMUC3[表皮生长因子（EGFR）阳性]和 T24（EGFR 低）细胞系和荷瘤小鼠。两种厄洛替尼缀合的 PSs 3 和 5 都表现出 EGFR 靶向特异性，但位置 3 的厄洛替尼 PS 缀合物 3 表现出比相应的非厄洛替尼类似物 1 更低的光动力治疗效果，而在 PS 的位置 17 处含有厄洛替尼部分的缀合物 5 显示出更高的肿瘤摄取率和长期肿瘤治愈（严重联合免疫缺陷小鼠荷 UMUC3 肿瘤）。缺乏光照的 PS-厄洛替尼缀合物在体外和体内均无效，但在将它们暴露于 665nm 激光光线下后，膀胱癌细胞中观察到强烈的细胞凋亡和坏死。与正电子发射断层扫描剂 F-氟脱氧葡萄糖不同，位置 17 的厄洛替尼缀合物（I-类似物 6）甚至在低成像剂量 15μCi/小鼠时也显示出增强的 UMUC3 肿瘤对比度。
