期刊
MOLECULAR PHARMACEUTICS
卷 8, 期 4, 页码 1186-1197出版社
AMER CHEMICAL SOC
DOI: 10.1021/mp200018y
关键词
photodynamic therapy; photosensitizer; HPPH; cRGD; cyclic Arg-Gly-Asp
资金
- NIH [CA127369]
- Roswell Park Alliance
- Roswell Park Cancer Center [CA16056]
The alpha(v)beta(3) integrin receptor plays an important role in human metastasis and tumor-induced angiogenesis. Cyclic Arg-Gly-Asp (cRGD) peptide represents a selective alpha(v)beta(3) 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-devinylpyro-pheophorbide a (HPPH), a chlorophyll-based photosensitizer, was conjugated to cRGD and the related analogues. The cell uptake and in vitro PDT efficacy of the conjugates were studied in alpha(v)beta(3) 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 nonconjugated 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 alpha(v)beta(3) integrin showed faster clearance, enhanced tumor imaging and enhanced PDT efficacy at 2-4 h postinjection. Molecular modeling studies also confirmed that the presence of the HPPH moiety in HPPH cRGD conjugate does not interfere with specific recognition of cRGD by alpha(v)beta(3) integrin. Compared to U87 and 4T1 cells the HPPH cRGD showed significantly low photosensitizing efficacy in alpha(v)beta(3) (alpha(v)beta(3) negative) tumor cells, suggesting possible target specificity of the conjugate.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据