Conjugation of cRGD peptide to chlorophyll a based photosensitizer (HPPH) alters its pharmacokinetics with enhanced tumor-imaging and photosensitizing (PDT) efficacy.
Conjugation of cRGD peptide to chlorophyll a based photosensitizer (HPPH) alters its pharmacokinetics with enhanced tumor-imaging and photosensitizing (PDT) efficacy.
复制标题
将CRGD肽与叶绿素A基光敏剂（HPPH）结合通过增强的肿瘤成像和光敏（PDT）功效来改变其药代动力学。
DOI：
10.1021/mp200018y
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发表时间：
2011-08-01
影响因子：
4.9
通讯作者：
Pandey RK
中科院分区：
文献类型：
--
作者：
Srivatsan A;Ethirajan M;Pandey SK;Dubey S;Zheng X;Liu TH;Shibata M;Missert J;Morgan J;Pandey RK
αvβ3整合素受体在人类转移和肿瘤诱导的血管生成中发挥重要作用。环精氨酸-甘氨酸-天冬氨酸 (cRGD) 肽代表一种选择性 αvβ3 整联蛋白配体，已广泛用于新血管生成的研究、治疗和诊断。为了开发具有增强PDT功效的光敏剂，我们在此报告了一系列双功能试剂的合成，其中3-(1'-己氧基乙基)-3-脱乙烯基焦脱镁叶绿酸-a (HPPH)，一种基于叶绿素的光敏剂与cRGD和相关类似物缀合。在αvβ3整合素过表达的U87和4T1细胞系中研究了缀合物的细胞摄取、体外PDT功效，而在4T1肿瘤中将缀合物的体内PDT功效和荧光成像潜力与相应的非缀合光敏剂HPPH进行了比较。与 HPPH 相比，精氨酸和天冬氨酸部分可与 αvβ3 整合素的两个亚基结合的 HPPH-cRGD 缀合物在注射后 2-4 小时显示出更快的清除速度、增强的肿瘤成像和 PDT 功效。分子模型研究还证实，HPPH-cRGD 缀合物中 HPPH 部分的存在不会干扰 αvβ3 整合素对 cRGD 的特异性识别。与 U87 和 4T1 细胞相比，HPPH-cRGD 在 A431（αvβ3 阴性）肿瘤细胞中表现出显着较低的光敏功效，表明缀合物可能具有靶点特异性。
The αvβ3 integrin receptor plays an important role in human metastasis and tumor-induced angiogenesis. Cyclic Arg-Gly-Asp (cRGD) peptide represents a selective αvβ3 integrin ligand that has been extensively used for research, therapy, and diagnosis of neoangiogenesis. For developing photosensitizers with enhanced PDT efficacy, we here report the synthesis of a series of bifunctional agents in which the 3-(1′-hexyloxyethyl)-3-devinylpyropheophorbide-a (HPPH), a chlorophyll-based photosensitizer was conjugated to cRGD and the related analogs. The cell uptake, in vitro PDT efficacy of the conjugates were studied in αvβ3 integrin overexpressing U87 and 4T1 cell lines whereas the in vivo PDT efficacy and fluorescence-imaging potential of the conjugates were compared with the corresponding non-conjugated photosensitizer HPPH in 4T1 tumors. Compared to HPPH, the HPPH-cRGD conjugate in which the arginine and aspartic acid moieties were available for binding to two subunits of αvβ3 integrin showed faster clearance, enhanced tumor-imaging and PDT efficacy at 2–4 h post-injection. Molecular modeling studies also confirmed that the presence of HPPH moiety in HPPH-cRGD conjugate does not interfere with specific recognition of cRGD by αvβ3 integrin. Compared to U87 and 4T1 cells the HPPH-cRGD showed significantly low photosensitizing efficacy in A431 (αvβ3 negative) tumor cells, suggesting possible target-specificity of the conjugate.
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影响因子：
6.4
作者：
Fabbrini, M;Trachsel, E;Neri, P
通讯作者：
Neri, P
影响因子：
3.1
作者：
Allen, CM;Sharman, WM;Weber, JM
通讯作者：
Weber, JM
影响因子：
11.2
作者：
Chen, XY;Conti, PS;Moats, RA
通讯作者：
Moats, RA
影响因子：
15.8
作者：
Haubner R;Weber WA;Beer AJ;Vabuliene E;Reim D;Sarbia M;Becker KF;Goebel M;Hein R;Wester HJ;Kessler H;Schwaiger M
通讯作者：
Schwaiger M
影响因子：
5
作者：
Castel, S;Pagan, R;Reina, M
通讯作者：
Reina, M