用于药物输送和磁共振成像应用的聚乙二醇功能化磁性纳米颗粒。

PEG-functionalized magnetic nanoparticles for drug delivery and magnetic resonance imaging applications.

机构信息

Department of Biomedical Engineering/ND-20 Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.

出版信息

Pharm Res. 2010 Nov;27(11):2283-95. doi: 10.1007/s11095-010-0260-1. Epub 2010 Sep 16.

PURPOSE

Polyethylene glycol (PEG) functionalized magnetic nanoparticles (MNPs) were tested as a drug carrier system, as a magnetic resonance imaging (MRI) agent, and for their ability to conjugate to an antibody.

METHODS

An iron oxide core coated with oleic acid (OA) and then with OA-PEG forms a water-dispersible MNP formulation. Hydrophobic doxorubicin partitions into the OA layer for sustained drug delivery. The T(1) and T(2) MRI contrast properties were determined in vitro and the circulation of the MNPs was measured in mouse carotid arteries. An N-hydroxysuccinimide group (NHS) on the OA-PEG-80 was used to conjugate the amine functional group on antibodies for active targeting in the human MCF-7 breast cancer cell line.

RESULTS

The optimized formulation had a mean hydrodynamic diameter of 184 nm with an ~8 nm iron-oxide core. The MNPs enhance the T(2) MRI contrast and have a long circulation time in vivo with 30% relative concentration 50 min post-injection. Doxorubicin-loaded MNPs showed sustained drug release and dose-dependent antiproliferative effects in vitro; the drug effect was enhanced with transferrin antibody-conjugated MNPs.

CONCLUSION

PEG-functionalized MNPs could be developed as a targeted drug delivery system and MRI contrast agent.

目的

聚乙二醇（PEG）功能化的磁性纳米颗粒（MNPs）被测试作为一种药物载体系统，作为磁共振成像（MRI）造影剂，并测试其与抗体结合的能力。

方法

用油酸（OA）涂覆的氧化铁核，然后用 OA-PEG 形成水可分散的 MNP 制剂。疏水性阿霉素分配到 OA 层中以进行持续的药物输送。在体外测定 T（1）和 T（2）MRI 对比特性，并在小鼠颈动脉中测量 MNPs 的循环。OA-PEG-80 上的 N-羟基琥珀酰亚胺基团（NHS）用于与抗体上的胺官能团结合，以在人 MCF-7 乳腺癌细胞系中进行主动靶向。

结果

优化的制剂具有 184nm 的平均水动力直径和约 8nm 的氧化铁核。MNPs 增强了 T（2）MRI 对比，并且在体内具有长的循环时间，在注射后 50 分钟时具有 30%的相对浓度。载有阿霉素的 MNPs 显示出持续的药物释放和体外剂量依赖性增殖抑制作用；转铁蛋白抗体偶联的 MNPs 增强了药物效果。