Long-circulating heparin-functionalized magnetic nanoparticles for potential application as a protein drug delivery platform.
Long-circulating heparin-functionalized magnetic nanoparticles for potential application as a protein drug delivery platform.
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DOI：
10.1021/mp400360q
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发表时间：
2013-10-07
影响因子：
4.9
通讯作者：
Yang VC
中科院分区：
文献类型：
--
作者：
Zhang J;Shin MC;David AE;Zhou J;Lee K;He H;Yang VC
成功地合成了淀粉包覆、聚乙二醇化和肝素功能化的氧化铁磁性纳米颗粒(DNPH)，并对其进行了详细的表征。聚乙二醇化(20 KDa)过程导致每个纳米颗粒平均包覆430个聚乙二醇分子。然后进行肝素偶联，得到肝素35.4μg/mg Fe的DNPH平台。商业上获得的肝素包裹的磁性纳米颗粒也被聚乙二醇化(HP)，并进行了表征以供比较。以鱼精蛋白为模型蛋白，证明DNPH与治疗相关阳离子蛋白具有很强的亲和力和较高的负载量。DNPH的最大负荷量为22.9μg鱼精蛋白/mg Fe。在药代动力学研究中，DNPH显示出9.37h的长循环半衰期，是HP(0.15h)的37.5倍。这种改善的血浆稳定性使DNPH能够更长时间地暴露于肿瘤病变中，这在磁共振成像(MRI)的侧翼9L胶质瘤小鼠模型中得到了直观证实。切除肿瘤组织中Fe含量的定量分析进一步证实了DNPH具有良好的肿瘤靶向性，最高可达31.36μg Fe/g组织(13.07%注射剂量(i.d.)/g组织)，是HP(4.27μg Fe/g组织；1.78%i.d./g组织)的7.5倍。总体而言，DNPH揭示了作为蛋白质药物输送平台的潜力。
Starch-coated, PEGylated and heparin-functionalized iron oxide magnetic nanoparticles (DNPH) were successfully synthesized and characterized in detail. The PEGylation (20 kDa) process resulted in an average coating of 430 PEG molecules per nanoparticle. After that, heparin conjugation was carried out to attain the final DNPH platform with 35.4 μg of heparin/mg Fe. Commercially acquired heparin-coated magnetic nanoparticles were also PEGylated (HP) and characterized for comparison. Protamine was selected as a model protein to demonstrate the strong binding affinity and high loading content of DNPH for therapeutically relevant cationic proteins. DNPH showed a maximum loading of 22.9 μg protamine/mg Fe. In the pharmacokinetic study, DNPH displayed a long-circulating half-life of 9.37 h, 37.5-fold longer than that (0.15 h) of H P. This improved plasma stability enabled extended exposure of DNPH to the tumor lesions, as was visually confirmed in a flank 9L-glioma mouse model using magnetic resonance imaging (MRI). Quantitative analysis of the Fe content in excised tumor lesions further demonstrated the superior tumor targeting ability of DNPH, with up to 31.36 μg Fe/g tissue (13.07% injected dose (I.D.)/g tissue) and 7.5-fold improvement over that (4.27 μg Fe/g tissue; 1.78% I.D./g tissue) of HP. Overall, DNPH shed light of the potential to be used as a protein drug delivery platform.
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