Synthesis, photophysical, electrochemical, tumor-imaging, and phototherapeutic properties of purpurinimide-N-substituted cyanine dyes joined with variable lengths of linkers.
Synthesis, photophysical, electrochemical, tumor-imaging, and phototherapeutic properties of purpurinimide-N-substituted cyanine dyes joined with variable lengths of linkers.
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DOI：
10.1021/bc200345p
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发表时间：
2011-11-16
影响因子：
4.7
通讯作者：
Pandey, Ravindra K.
中科院分区：
文献类型：
--
作者：
Williams, Michael P. A.;Ethirajan, Manivannan;Ohkubo, Kei;Chen, Ping;Pera, Paula;Morgan, Janet;White, William H., III;Shibata, Masayuki;Fukuzumi, Shunichi;Kadish, Karl M.;Pandey, Ravindra K.
具有不同长度的 N-取代基的紫嘌呤酰亚胺甲酯分别与具有羧酸官能团的花青染料缀合。体外和体内研究获得的结果表明连接光疗和荧光成像部分的连接体具有显着影响。带有 PEG 连接体的光敏剂-荧光团缀合物在肝脏中显示出最高的吸收，而与两个碳单元连接的缀合物在注射后 24 小时显示出优异的肿瘤成像和 PDT 功效。不同时间点的全身成像和生物分布研究表明，与皮肤相比，肿瘤中缀合物的荧光摄取增强。有趣的是，具有最短连接体的缀合物和与两个碳单元连接的缀合物显示出从正常器官（例如）更快的清除。例如，肝、肾、脾、肺与肿瘤的比较。缀合物的成像和 PDT 功效均在携带 Colon26 肿瘤的 BALB/c 小鼠中进行。与其他缀合物相比，短接头缀合物显示出较差的肿瘤荧光特性，并且推论不表现出光敏剂-荧光团缀合物的双重功能。因此，未对其体内 PDT 功效进行评估。然而，在 Colon26 肿瘤细胞（体外）中，短接头非常有效。在具有可变接头的缀合物中，从紫嘌呤亚胺部分到花青部分的能量转移速率随着接头长度的减小而增加，如通过飞秒激光闪光光解测量所检测的。通过将瞬态吸收光谱与通过光谱电化学测量获得的缀合物的一电子氧化和一电子还原物质的光谱进行比较表明，没有发生从紫红酰亚胺部分到花青部分的单重激发态或从花青部分的单重激发态到红紫酰亚胺部分的电子转移。
Purpurinimide methyl esters, bearing variable lengths of N-substitutions, were conjugated individually to a cyanine dye with a carboxylic acid functionality. The results obtained from in vitro and in vivo studies showed a significant impact of the linkers joining the phototherapeutic and fluorescence imaging moieties. The photosensitizer-fluorophore conjugate with a PEG linker showed the highest uptake in the liver, whereas the conjugate linked with two carbon units showed excellent tumor-imaging and PDT efficacy at 24 h postinjection. Whole body imaging and biodistribution studies at variable time points portrayed enhanced fluorescent uptake of the conjugates in the tumor compared to the skin. Interestingly the conjugate with the shortest linker and the one joining with two carbon units showed faster clearance from normal organs e. g., liver, kidney, spleen, lung compared to tumors. Both imaging and PDT efficacy of the conjugates were performed in BALB/c mice bearing Colon26 tumors. Compared to the others, the short linker conjugate showed poor tumor fluorescent properties and as a corollary does not exhibit the dual functionality of the photosensitizer-fluorophore conjugate. For this reason, it was not evaluated for in vivo PDT efficacy. However, in Colon26 tumor cells (in vitro), the short linker was highly effective. Among the conjugates with variable linkers, the rate of energy transfer from the purpurinimide moiety to the cyanine moiety increased with deceasing linker length, as examined by femtosecond laser flash photolysis measurements. No electron transfer from the purpurinimide moiety to the singlet excited state of the cyanine moiety or from the singlet excited state of the cyanine moiety to the purpurinimide moiety occurred as indicated by a comparison of transient absorption spectra with spectra of the one-electron oxidized and one-electron reduced species of the conjugate obtained by spectroelectrochemical measurements.
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影响因子：
4.7
作者：
Mujumdar, SR;Mujumdar, RB;Waggoner, AS
通讯作者：
Waggoner, AS
影响因子：
4.3
作者：
Ornelas, Catia;Lodescar, Rachelle;Weck, Marcus
通讯作者：
Weck, Marcus
影响因子：
4.9
作者：
Pandey, Suresh K.;Zheng, Xiang;Pandey, Ravindra K.
通讯作者：
Pandey, Ravindra K.
影响因子：
3.6
作者：
NARAYANAN, N;PATONAY, G
通讯作者：
PATONAY, G
影响因子：
4.7
作者：
Chen, YH;Gryshuk, A;Pandey, RK
通讯作者：
Pandey, RK