Jain Tapan K, Richey John, Strand Michelle, Leslie-Pelecky Diandra L, Flask Chris A, Labhasetwar Vinod
Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Biomaterials. 2008 Oct;29(29):4012-21. doi: 10.1016/j.biomaterials.2008.07.004. Epub 2008 Jul 22.
There is significant interest in recent years in developing magnetic nanoparticles (MNPs) having multifunctional characteristics with complimentary roles. In this study, we investigated the drug delivery and magnetic resonance imaging (MRI) properties of our novel oleic acid-coated iron-oxide and pluronic-stabilized MNPs. The drug incorporation efficiency of doxorubicin and paclitaxel (alone or in combination) in MNPs was 74-95%; the drug release was sustained and the incorporated drugs had marginal effects on physical (size and zeta potential) and magnetization properties of the MNPs. The drugs in combination incorporated in MNPs demonstrated highly synergistic antiproliferative activity in MCF-7 breast cancer cells. The T2 relaxivity (r(2)) was higher for our MNPs than Feridex IV, whereas the T1 relaxivity (r(1)) was better for Feridex IV than for our MNPs, suggesting greater sensitivity of our MNPs than Feridex IV in T2 weighted imaging. The circulation half-life (t(1/2)), determined from the changes in the MRI signal intensity in carotid arteries in mice, was longer for our MNPs than Feridex IV (t(1/2)=31.2 vs. 6.4 min). MNPs with combined characteristics of MRI and drug delivery could be of high clinical significance in the treatment of various disease conditions.
近年来,人们对开发具有互补作用的多功能磁性纳米颗粒(MNP)有着浓厚的兴趣。在本研究中,我们研究了新型油酸包覆的氧化铁和普朗尼克稳定的MNP的药物递送和磁共振成像(MRI)特性。阿霉素和紫杉醇(单独或联合使用)在MNP中的药物包封效率为74-95%;药物释放是持续的,并且所包封的药物对MNP的物理性质(尺寸和zeta电位)和磁化性质影响很小。包封在MNP中的联合药物在MCF-7乳腺癌细胞中表现出高度协同的抗增殖活性。我们的MNP的T2弛豫率(r(2))高于Feridex IV,而Feridex IV的T1弛豫率(r(1))优于我们的MNP,这表明在T2加权成像中我们的MNP比Feridex IV具有更高的灵敏度。根据小鼠颈动脉MRI信号强度的变化确定的循环半衰期(t(1/2)),我们的MNP比Feridex IV更长(t(1/2)=31.2对6.4分钟)。具有MRI和药物递送联合特性的MNP在各种疾病的治疗中可能具有很高的临床意义。