A small molecular “albumin hitchhiking” Deferoxamine conjugate improved iron clearance efficacy

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
出处
期刊:Journal of Drug Delivery Science and Technology [Elsevier]
卷期号:97: 105793-105793
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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