Development of Glycoconjugated Porphyrin Derivatives for Photodynamic Therapy

1.糖缀合卟啉衍生物的新合成策略为了提高糖缀合卟啉衍生物，特别是间取代四苯基卟啉衍生物的收率，研究了Zn2+离子模板法。此外，演示了糖缀合氯衍生物的RP-TLC纯化，以去除伴随的副产物，糖缀合卟啉和细菌氯衍生物。因此，在光动力治疗中，糖缀合卟啉和氯衍生物的生产规模和纯度均达到了一定的要求。糖缀合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。用反相高效液相色谱法测定了糖缀合卟啉衍生物的疏水性。2 .发现了明显的依赖性疏水性。体外光毒试验前，采用荧光法测定HeLa细胞对糖缀合卟啉衍生物的细胞摄取量。吸收量与附着糖单位有显著关系，而疏水性与细胞吸收量无明显相关性。糖缀合卟啉衍生物的体外光毒性试验对具有较高细胞摄取量的糖缀合卟啉衍生物进行了初步的体外光毒性试验。虽然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。这些结果提示糖调节PDT光细胞毒性的可能性。

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.