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Development of Glycoconjugated Porphyrin Derivatives for Photodynamic Therapy

用于光动力治疗的糖基卟啉衍生物的开发

基本信息

批准号：
13557211
负责人：
YANO Shiganobu
金额：
$ 8.64万
依托单位：
Nara Women's University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13557211/
关键词：
Sugar Photosensitizer Photodynamic Therapy PDT ポルフィリンクロリン HeLa cell S180 sarcoma cell KLN205 squamous cel 光線力学的療法バクテリオクロリン一重項酸素発生光毒性 HeLa細胞

项目摘要

1.Novel Synthetic Strategy for Glycoconjuated Porphyrin DerivativesIn order to improve the yield of glycoconjugated porphyrin derivatives, especially for meta-substituted tetraphenyl porphyrin, Zn2+ ion template methodology had been developed. In addition, demonstrate the RP-TLC purification of glycoconjugated chlorin derivatives to remove concomitant by-product, glycoconjugated porphyrin and bacteriochlorin derivatives. So now glycoconjugated porphyrin and chlorin derivatives can be produced in applicable scale and purity in photodynamic therapy.2.Estimation of Hydrophobicity of Glycoconjugated Porphyrin DerivativesHyrophobicity is fundamental characteristic for pharmakokinetics. We demonstrated the estimation of hydrophobicity of glycoconjugated porphyrin derivatives by means of reversed phase HPLC method. Significant sugedependent hydrophobicity was found clearly.3.Cellular Uptake of Glycoconjugated Porphyrin Derivatives by HeLa cellsPrior to in vitro photocytotoxicity test, the cellular uptake amount of glycoconjugated porphyrin derivatives by HeLa cells was determined by means of fluorometry. The uptake amount significantly depended on sugar unit attached, However, no apprent correlation between hydrophobicity and cellular uptake was found.4.In vitro Photocytotoxicity Test for Glycoconjugated Porphyrin DerivativesPreliminary in vitro photocytotoxicity test was performed for glycoconjugated porphyrin derivatives which exerted higher amount of cellular uptake. Even though the photocytotoxicity was not connected to the cellular uptake amount, photocytotoxicity highly depended on sugar unit attached. These results suggest the possibility of glyco-regulation of photocytotoxicity in PDT.

1.糖基卟啉衍生物的新合成策略为了提高糖基卟啉衍生物的产率，特别是间位取代的四苯基卟啉，开发了Zn2+离子模板法。此外，展示了糖缀合二氢卟酚衍生物的 RP-TLC 纯化，以去除伴随的副产物、糖缀合卟啉和菌绿素衍生物。因此，现在可以以适合光动力治疗的规模和纯度生产糖基卟啉和二氢卟酚衍生物。2.糖基卟啉衍生物的疏水性估计疏水性是药代动力学的基本特征。我们展示了通过反相 HPLC 方法评估糖缀合卟啉衍生物的疏水性。明显地发现了显着的糖依赖性疏水性。3.HeLa细胞对糖基卟啉衍生物的细胞摄取在体外光细胞毒性试验之前，采用荧光法测定HeLa细胞对糖基卟啉衍生物的细胞摄取量。摄取量明显取决于所附着的糖单元，但疏水性与细胞摄取之间没有发现明显的相关性。4.糖基卟啉衍生物的体外光细胞毒性试验对细胞摄取量较高的糖基卟啉衍生物进行了初步的体外光细胞毒性试验。尽管光细胞毒性与细胞摄取量无关，但光细胞毒性高度依赖于附着的糖单元。这些结果表明 PDT 中光细胞毒性的糖调节的可能性。