Assessing Photosensitizer Targeting Using Meso-Tetra(Carboxyphenyl) Porphyrin.
Assessing Photosensitizer Targeting Using Meso-Tetra(Carboxyphenyl) Porphyrin.
复制标题
DOI：
10.3390/molecules23040892
复制
发表时间：
2018-04-12
期刊：
影响因子：
--
通讯作者：
Rajendiran V
中科院分区：
文献类型：
--
作者：
Chitgupi U;Lovell JF;Rajendiran V
中位四（4-羧基苯基）卟啉（Mesotetra（4-carboxyphenyl）porphyrin，mTCPP）是一种具有四个自由羧酸基团的小分子荧光团和光敏剂。mTCPP可以容易地与胺缀合以便于官能团的连接。在这项工作中，我们合成和评估四价，赖氨酸共轭mTCPP，其潜在的应用在靶向成像和光动力治疗。Fmoc保护的d-赖氨酸或l-赖氨酸通过与赖氨酸的N-氨基偶联的酰胺偶联与mTCPP缀合，然后进行Fmoc脱保护。所得化合物在水性溶剂中溶解不良，但可在表面活性剂（包括胆酸）的帮助下增溶。L-氨基酸转运蛋白（LAT 1）可摄取多种中性L-氨基酸。U87细胞的体外研究揭示了疏水性Fmoc保护的赖氨酸缀合的mTCPP前体的非特异性摄取，但不是d-或l-赖氨酸mTCPP。同样，只有Fmoc保护的化合物在孵育和蓝光照射后诱导细胞中的大量光毒性。这些实验结果没有提供证据表明赖氨酸-mTCPP能够特异性靶向癌细胞。然而，他们确实强调mTCPP是评估光敏剂分子靶向的方便和可访问的框架。
Mesotetra(4-carboxyphenyl)porphyrin (mTCPP) is a commercially available small molecule fluorophore and photosensitizer with four free carboxylic acid groups. mTCPP can readily be conjugated with amines for facile attachment of functional groups. In this work, we synthesized and assessed tetravalent, lysine-conjugated mTCPP, for its potential applications in targeted imaging and photodynamic therapy. Fmoc-protected d-lysine or l-lysine was conjugated to mTCPP via amide coupling with the epsilon amine group of lysine, followed by Fmoc deprotection. The resulting compounds did not dissolve well in aqueous solvent, but could be solubilized with the assistance of surfactants, including cholic acid. The l-amino acid transporter (LAT1) can uptake diverse neutral l-amino acids. In vitro studies with U87 cells revealed a non-specific uptake of the hydrophobic Fmoc-protected lysine-conjugated mTCPP precursors, but not d- or l-lysine mTCPP. Likewise, only the Fmoc-protected compounds induced substantial phototoxicty in cells following incubation and irradiation with blue light. These experimental results do not provide evidence to suggest that lysine-mTCPP is able to specifically target cancer cells. However, they do highlight mTCPP as a convenient and accessible framework for assessing molecular targeting of photosensitizers.
登录
查看更多内容
DOI：
10.3322/caac.20114
发表时间：
2011-07
期刊：
CA: a cancer journal for clinicians
影响因子：
--
作者：
Agostinis P;Berg K;Cengel KA;Foster TH;Girotti AW;Gollnick SO;Hahn SM;Hamblin MR;Juzeniene A;Kessel D;Korbelik M;Moan J;Mroz P;Nowis D;Piette J;Wilson BC;Golab J
通讯作者：
Golab J
影响因子：
--
作者：
Chitgupi U;Qin Y;Lovell JF
通讯作者：
Lovell JF
影响因子：
7.3
作者：
Josefsen, L. B.;Boyle, R. W.
通讯作者：
Boyle, R. W.
影响因子：
14
作者：
Huang H;Hernandez R;Geng J;Sun H;Song W;Chen F;Graves SA;Nickles RJ;Cheng C;Cai W;Lovell JF
通讯作者：
Lovell JF
影响因子：
3.1
作者：
Huh, Seong;Kim, Sung-Jin;Kim, Youngmee
通讯作者：
Kim, Youngmee