A porphyrin-PEG polymer with rapid renal clearance.
A porphyrin-PEG polymer with rapid renal clearance.
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DOI：
10.1016/j.biomaterials.2015.10.049
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发表时间：
2016-01
期刊：
影响因子：
14
通讯作者：
Lovell JF
中科院分区：
文献类型：
--
作者：
Huang H;Hernandez R;Geng J;Sun H;Song W;Chen F;Graves SA;Nickles RJ;Cheng C;Cai W;Lovell JF
四羧酸卟啉和聚乙二醇（PEG）二胺交联的条件下，产生水溶性卟啉聚酰胺。使用2kDa或更大的PEG接头防止荧光自猝灭。在用具有100 kDa孔径的膜透析期间保留这种网状卟啉网，但当应用离心过滤时通过膜。静脉内给药后，卟啉网，但不是游离卟啉，通过肾脏排泄迅速清除。该过程可以通过对收集的尿液进行荧光分析来监测，由于卟啉的大斯托克斯位移（230 nm分离激发和发射峰）而具有最小的背景。在横纹肌溶解症小鼠肾衰竭模型中，卟啉网状物尿清除率显著受损。这导致膀胱中的积聚较慢，这可以通过荧光成像非侵入性地可视化。在没有进一步修改的情况下，卟啉网与64 Cu螯合，用于肾清除率的动态全身正电子发射断层扫描成像。总之，这些数据表明，小卟啉-PEG聚合物可以作为肾功能的有效多模式标志物。
Tetracarboxylic porphyrins and polyethylene glycol (PEG) diamines were crosslinked in conditions that gave rise to a water-soluble porphyrin polyamide. Using PEG linkers 2 kDa or larger prevented fluorescence self-quenching. This networked porphyrin mesh was retained during dialysis with membranes with a 100 kDa pore size, yet passed through the membrane when centrifugal filtration was applied. Following intravenous administration, the porphyrin mesh, but not the free porphyrin, was rapidly cleared via renal excretion. The process could be monitored by fluorescence analysis of collected urine, with minimal background due to the large Stokes shift of the porphyrin (230 nm separating excitation and emission peaks). In a rhabdomyolysis mouse model of renal failure, porphyrin mesh urinary clearance was significantly impaired. This led to slower accumulation in the bladder, which could be visualized non-invasively via fluorescence imaging. Without further modification, the porphyrin mesh was chelated with 64Cu for dynamic whole body positron emission tomography imaging of renal clearance. Together, these data show that small porphyrin-PEG polymers can serve as effective multimodal markers of renal function.