Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnosis, School of Pharmacy, Tianjin Medical University , Tianjin 300070, China.
Mol Pharm. 2013 Oct 7;10(10):3892-902. doi: 10.1021/mp400360q. Epub 2013 Sep 11.
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 of 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 of protamine/mg of 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 HP. 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 of Fe/g of tissue (13.07% injected dose (I.D.)/g of tissue) and 7.5-fold improvement over that (4.27 μg of Fe/g of tissue; 1.78% I.D./g of tissue) of HP. Overall, this study shed light on the potential of DNPH to be used as a protein drug delivery platform.
淀粉包覆的、聚乙二醇化的、肝素功能化的氧化铁磁性纳米颗粒（DNPH）被成功合成并进行了详细的表征。PEG 化（20 kDa）过程导致每个纳米颗粒平均包覆 430 个 PEG 分子。之后，进行肝素接枝，得到最终的 DNPH 平台，其铁含量为 35.4μg/mg。还对商业获得的肝素包覆的磁性纳米颗粒（HP）进行了 PEG 化并进行了特征分析以作比较。鱼精蛋白被选为模型蛋白，以证明 DNPH 对治疗相关阳离子蛋白具有很强的结合亲和力和高载药含量。DNPH 的最大载药量为 22.9μg/mg 的铁。在药代动力学研究中，DNPH 表现出 9.37 h 的长循环半衰期，比 HP（0.15 h）长 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灶中，这在使用磁共振成像（MRI）的侧腹 9L 神经胶质瘤小鼠模型中得到了直观证实。对切除的肿瘤病灶中 Fe 含量的定量分析进一步证明了 DNPH 的优越的肿瘤靶向能力，其铁含量高达 31.36μg/g 组织（13.07%注射剂量（ID）/g 组织），比 HP（4.27μg/g 组织；1.78%ID/g 组织）提高了 7.5 倍。总的来说，这项研究揭示了 DNPH 作为蛋白质药物递送平台的潜力。
