Do Ton Duc, Ul Amin Faiz, Noh Yeongil, Kim Myeong Ok, Yoon Jungwon
J Biomed Nanotechnol. 2016 Mar;12(3):569-74. doi: 10.1166/jbn.2016.2193.
The "impermeability" of the blood-brain barrier (BBB) has hindered effective treatment of central nervous system (CNS) disorders such as Alzheimer's disease (AD), which is one of the most common neurodegenerative disorders. A drug can be delivered to a targeted disease site effectively by applying a strong electromagnetic force to the conjugate of a drug and magnetic nanocontainers. This study developed a novel nanotechnology-based strategy to deliver therapeutic agents to the brain via the BBB as a possible therapeutic approach for AD. First, a novel approach for an electromagnetic actuator for guiding nanocontainers is introduced. Then, we analyzed the in vivo uptake in mice experimentally to evaluate the capacity of the nanocontainers. In the mouse model, we demonstrated that magnetic particles can cross the normal BBB when subjected to external electromagnetic fields of 28 mT (0.43 T/m) and 79.8 mT (1.39 T/m). Our study also assessed the differential effects of pulsed (0.25, 0.5, and 1 Hz) and constant magnetic fields on the transport of particles across the BBB in mice injected with magnetic nanoparticles (MNPs) via a tail vein. The applied magnetic field was either kept constant or pulsed on and off. Relative to a constant magnetic field, the rate of MNP uptake and transport across the BBB was enhanced significantly by a pulsed magnetic field. Localization inside the brain was established using fluorescent MNPs. These results using 770-nm fluorescent carboxyl magnetic nanocontainers demonstrated the feasibility of the proposed electromagnetic targeted drug delivery actuator. These results establish an effective strategy for regulating the biodistribution of MNPs in the brain through the application of an external electromagnetic field. This might be a valuable targeting system for AD diagnosis and therapy.
血脑屏障（BBB）的“不渗透性”阻碍了对中枢神经系统（CNS）疾病（如阿尔茨海默病（AD），这是最常见的神经退行性疾病之一）的有效治疗。通过对药物与磁性纳米容器的共轭物施加强电磁力，可以将药物有效地递送至靶向疾病部位。本研究开发了一种基于纳米技术的新策略，通过血脑屏障将治疗剂递送至大脑，作为治疗AD的一种可能方法。首先，介绍了一种用于引导纳米容器的新型电磁致动器方法。然后，我们通过实验分析了小鼠体内的摄取情况，以评估纳米容器的能力。在小鼠模型中，我们证明当受到28 mT（0.43 T/m）和79.8 mT（1.39 T/m）的外部电磁场作用时，磁性颗粒可以穿过正常的血脑屏障。我们的研究还评估了脉冲（0.25、0.5和1 Hz）和恒定磁场对经尾静脉注射磁性纳米颗粒（MNPs）的小鼠体内颗粒穿过血脑屏障运输的不同影响。施加的磁场要么保持恒定，要么脉冲式开关。相对于恒定磁场，脉冲磁场显著提高了MNPs摄取和穿过血脑屏障的运输速率。使用荧光MNPs确定了其在脑内的定位。这些使用770 nm荧光羧基磁性纳米容器的结果证明了所提出的电磁靶向药物递送致动器的可行性。这些结果建立了一种通过施加外部电磁场来调节MNPs在脑内生物分布的有效策略。这可能是用于AD诊断和治疗的有价值的靶向系统。
