Design of Bifunctional Dendritic 5-Aminolevulinic Acid and Hydroxypyridinone Conjugates for Photodynamic Therapy,Bioconjugate Chemistry

当前位置： X-MOL 学术 › Bioconjugate Chem. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Design of Bifunctional Dendritic 5-Aminolevulinic Acid and Hydroxypyridinone Conjugates for Photodynamic Therapy
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2018-09-24 00:00:00 , DOI: 10.1021/acs.bioconjchem.8b00574
Tao Zhou ₁ , Sinan Battah _{2,

3} , Francesca Mazzacuva ₄ , Robert C Hider ₄ , Paul Dobbin ₂ , Alexander J MacRobert ₃

Affiliation

Iron chelators have recently attracted interest in the field of photodynamic therapy (PDT) owing to their role in enhancement of intracellular protoporphyrin IX (PpIX) generation induced by 5-aminolevulinic acid (ALA) via the biosynthetic heme cycle. Although ALA is widely used in PDT, cellular uptake of ALA is limited by its hydrophilicity. In order to improve ALA delivery and enhance the PpIX production, several dendrimers incorporating both ALA and 3-hydroxy-4-pyridinone (HPO) were synthesized. The ability of the dendrimers to enter cells and be metabolized to the PpIX photosensitizer was studied in several human cancer cell lines. The dendrimers were found to be significantly more efficient than ALA alone in PpIX production. The higher intracellular PpIX levels showed a clear correlation with enhanced cellular phototoxicity following light exposure. Dendritic derivatives are therefore capable of efficiently delivering both ALA and HPO, which act synergistically to amplify in vitro PpIX levels and enhance PDT efficacy.

中文翻译：

用于光动力治疗的双功能树枝状 5-氨基乙酰丙酸和羟基吡啶酮缀合物的设计

铁螯合剂最近引起了光动力疗法 (PDT) 领域的兴趣，因为它们在增强 5-氨基乙酰丙酸 (ALA) 通过生物合成血红素循环诱导的细胞内原卟啉 IX (PpIX) 生成方面发挥作用。尽管 ALA 广泛用于 PDT，但 ALA 的细胞摄取因其亲水性而受到限制。为了改善 ALA 递送并增强 PpIX 产量，合成了几种结合 ALA 和 3-羟基-4-吡啶酮 (HPO) 的树枝状聚合物。在几种人类癌细胞系中研究了树枝状聚合物进入细胞并代谢为 PpIX 光敏剂的能力。发现树枝状聚合物在 PpIX 生产中比单独使用 ALA 更有效。较高的细胞内 PpIX 水平显示出与光照后细胞光毒性增强的明显相关性。因此，树突状衍生物能够有效地递送 ALA 和 HPO，它们协同作用以放大体外PpIX 水平并增强 PDT 功效。

更新日期：2018-09-24

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11