Hydroxypyridinone and 5-Aminolaevulinic Acid Conjugates for Photodynamic Therapy
Hydroxypyridinone and 5-Aminolaevulinic Acid Conjugates for Photodynamic Therapy
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DOI：
10.1021/acs.jmedchem.7b00346
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发表时间：
2017-04-27
影响因子：
7.3
通讯作者：
Zhou, Tao
中科院分区：
文献类型：
--
作者：
Battah, Sinan;Hider, Robert C.;Zhou, Tao
光动力疗法（PDT）是一种很有前途的治疗恶性和非恶性病变的策略。5-氨基乙酰丙酸（ALA）被用作光敏剂原卟啉IX （PpIX）的前体，用于皮肤病学和泌尿学。然而，ALA- pdt的有效性受到ALA相对较差的生物利用度的限制。以及PpIX到haem的快速转换。本研究的主要目的是制备和研究一个设计用于共同给药的生物活性药物的单缀合物文库。ALA和羟基吡啶酮（HPO）铁螯合剂。与单独服用ALA相比，在所有细胞系中均观察到细胞内PpIX水平的显著增加。使用共轭物观察到的较高PpIX水平与细胞暴露于光后观察到的光毒性密切相关。被动扩散似乎是大多数ALA-HPOs研究的主要机制。本研究表明，ALA-HPOs可显著增强光疗代谢物的形成和光毒性。
Photodynamic therapy (PDT) is a promising treatment strategy for malignant and nonmalignant lesions. 5-Aminolaevulinic acid (ALA) is used as a precursor of the photosensitizer, protoporphyrin IX (PpIX), in dermatology and urology. However, the effectiveness of ALA-PDT is limited by the relatively poor bioavailability of ALA. and rapid conversion of PpIX to haem. The main goal of this study was to prepare and investigate a library of single conjugates designed to coadminister the bioactive agents. ALA and hydroxypyridinone (HPO) iron chelators. A significant increase in intracellular PpIX levels was observed in all cell lines tested when compared to the administration of ALA alone. The higher PpIX levels observed using the conjugates correlated well with the observed phototoxicity following exposure of cells to light. Passive diffusion appears to be the main mechanism for the majority of ALA-HPOs investigated. This study demonstrates that ALA-HPOs significantly enhance phototherapeutic metabolite foiniation and phototoxicity.