School of Food Science and Biotechnology , Zhejiang Gongshang University , Hangzhou , Zhejiang 310035 , P.R. China.
School of Biological Sciences , University of Essex , Wivenhoe Park , Colchester CO4 3SQ , U.K.
Bioconjug Chem. 2018 Oct 17;29(10):3411-3428. doi: 10.1021/acs.bioconjchem.8b00574. Epub 2018 Oct 5.
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.
铁螯合剂由于在通过生物合成血红素循环增强 5-氨基酮戊酸 (ALA) 诱导的细胞内原卟啉 IX (PpIX) 生成方面的作用，最近在光动力疗法 (PDT) 领域引起了关注。尽管 ALA 在 PDT 中被广泛应用，但由于其亲水性，ALA 的细胞摄取受到限制。为了提高 ALA 的递送并增强 PpIX 的产生，合成了几种同时包含 ALA 和 3-羟基-4-吡啶酮 (HPO) 的树状大分子。研究了树状大分子进入细胞并代谢为光敏剂 PpIX 的能力在几种人癌细胞系中。与单独使用 ALA 相比，树状大分子在 PpIX 生成方面明显更有效。较高的细胞内 PpIX 水平与光暴露后增强的细胞光毒性之间存在明显的相关性。因此，树枝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 效果。
