Improvement of meta-tetra(hydroxyphenyl)chlorin-like photosensitizer selectivity with folate-based targeted delivery.: Synthesis and in vivo delivery studies

被引：115

作者：

Gravier, Julien ^{[2
]}

Schneider, Raphael ^{[1
]}

Frochot, Celine ^{[1
]}

Bastogne, Thierry ^{[3
]}

Schmitt, Frederic

Didelon, Jacques ^{[4
]}

Guillemin, Francois ^{[3
]}

Barberi-Heyob, Muriel ^{[3
]}

机构：

[1] Nancy Univ, CNRS, DCPR, Dept Chim Phys React, F-54001 Nancy, France

[2] Nancy Univ, SRSMC, F-54506 Vandoeuvre Les Nancy, France

[3] Nancy Univ, CNRS, CAV, CRAN, F-54511 Vandoeuvre Les Nancy, France

[4] Nancy Univ, Univ Inst Pathol, CHUV, CAV, CH-1011 Lausanne, Switzerland

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 51卷 / 13期

关键词：

D O I：

10.1021/jm800125a

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The cell membrane folate receptor (FR) is a molecular target for tumor-selective drug delivery, including delivery of photosensitizers for anticancer photodynamic therapy (PDT). Tumor selectivity of metatetra(hydroxyphenyl)chlorin (m-THPC), a photosensitizer used in PDT clinical trials, demonstrates a low tumor-to-normal epithelial uptake ratio. We report on the synthesis and on the photophysical properties of a m-THPC-like photosensitizer I conjugated to folic acid (compound 8). A comparative study of the accumulation of photosensitizers I and 8 is described. Nude mice were xenografted with FR-alpha-positive KB or HT-29 cells lacking FR-alpha as a negative control. Using optical fiber fluorimetry, we demonstrated that conjugate 8 exhibited enhanced accumulation in KB tumors compared to 14 h after injection. No significant difference between KB and HT-29 tumors was observed in case of compound 1. Tumor-to-normal tissue ratio exhibited a very interesting selectivity for conjugate 8 (5: 1) in KB tumors 4 h postinjection.

引用

页码：3867 / 3877

页数：11

共 68 条

[11] Foscan® uptake and tissue distribution in relation to photodynamic efficacy [J].