去铁胺
结合
白蛋白
化学
生物物理学
医学
材料科学
生物化学
生物
数学
数学分析
作者
Linyi Xu,Yingxi Zhang,Yue Wang,Ning Li,Yicheng Li,Weijia Huang,Yang Yang,Yongjun Wang,Hongzhuo Liu
标识
DOI:10.1016/j.jddst.2024.105793
摘要
Deferoxamine (DFO), the first FDA-approved iron chelator, showed multifaceted potential in the treatment of iron accumulation-related diseases. However, the extremely short half-life of DFO leads to low patient compliance, and required high doses result in nonspecific toxicity. To overcome these obstacles, a new conjugate 2-sulfo-9-fluorenylmethoxycarbonyl-deferoxamine (FMS-DFO) was developed, which could be leveraged to hand-in-hand associate with the albumin in plasma to bypass the rapid elimination and reduce the related toxicities. FMS-DFO was observed in comparable albumin binding capacity as the amphiphilic modular "albumin hitchhiking" DSPE-PEG2000-DFO and maintained identical iron chelating potency of DFO. As compared with DSPE-PEG2000-DFO (t1/2 ∼ 1.30 h), FMS-DFO (t1/2 ∼ 4.49 h) remarkably more prolonged the exposure circulation of marketed DFO (t1/2 ∼ 0.08 h) in mice. FMS-DFO could spare the dosing frequency from 5 times to 3 times weekly in iron overload therapy, which can improve patient compliance and reduce the difficulty of clinical usage. Additionally, the combined utilization of 5-ALA and FMS-DFO demonstrated excellent anti-cancer efficacy in synergistic photodynamic therapy model, broadening the clinical potential of the developed iron chelators. The strategy of "albumin hitchhiking" FMS-DFO is thus of great clinical interest and merits further exploration for treating iron accumulation-related diseases.
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