Yin Xuanying, Qiu Jinmei, Cheng Guowang, Wu Jiaxin, Wang Chen, Zheng Chunye, Huang Shuiqing, Chen Tongkai
Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, 12 Jichang Road, Guangzhou, 510405, China.
Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China.
Chin Med. 2025 Nov 8;20(1):185. doi: 10.1186/s13020-025-01239-2.
Parkinson's disease (PD) has emerged as a critical public health challenge amidst global population aging. The pathogenesis of PD is extremely complex. Notably, evidence showed that neuroinflammation due to microglial activation is a critical driver of dopaminergic neuron loss in patients with PD. Therefore, several strategies aimed at alleviating neuroinflammation are currently being tested for the treatment of PD. However, current anti-inflammatory agents exhibit limited therapeutic efficacy in vivo due to hindrances caused by the blood-brain barrier (BBB). To overcome BBB-related challenges, we developed a biomimetic nanodelivery system (DCM@Nar-NCs) by encapsulating naringenin nanocrystals (Nar-NCs) within differentiated HL-60 cell membranes. Our analysis demonstrated that DCM@Nar-NCs could act as an innovative nanoplatform for PD therapy, showing BBB penetration capabilities and exhibiting precise accumulation at sites of neuroinflammation. This targeted delivery enables more precise and potent treatment than existing therapeutic modalities.
The BBB penetration efficiency and brain-targeted delivery of DCM@Nar-NCs were assessed both in vitro and in vivo. The neuroprotective effects were comprehensively investigated in cellular and animal levels. Finally, the ability of DCM@Nar-NCs to ameliorate motor dysfunction and cognitive impairment was validated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse models.
DCM@Nar-NCs exhibited significantly enhanced BBB permeability and could exert dual therapeutic effects. Notably, DCM@Nar-NCs modulated microglial polarization (pro-inflammatory M1 phenotype to neuroprotective M2 phenotype), thereby attenuating neuroinflammatory cascades. Additionally, DCM@Nar-NCs could ameliorate mitochondrial dysfunction and thereby prevent the apoptosis and destruction of dopaminergic neurons. Finally, behavioral assessments in animal models confirmed the remarkable capacity of DCM@Nar-NCs to reverse PD-related motor deficits and cognitive impairment.
Collectively, the novel PD treatment approach developed in this study offers superior biosafety and treatment efficacy, highlighting its strong potential for clinical translation.
在全球人口老龄化的背景下，帕金森病（PD）已成为一项严峻的公共卫生挑战。PD的发病机制极其复杂。值得注意的是，有证据表明，小胶质细胞激活引起的神经炎症是PD患者多巴胺能神经元丢失的关键驱动因素。因此，目前正在测试几种旨在减轻神经炎症的策略用于PD的治疗。然而，由于血脑屏障（BBB）造成的阻碍，目前的抗炎药物在体内的治疗效果有限。为了克服与BBB相关的挑战，我们通过将柚皮素纳米晶体（Nar-NCs）包裹在分化的HL-60细胞膜内，开发了一种仿生纳米递送系统（DCM@Nar-NCs）。我们的分析表明，DCM@Nar-NCs可以作为一种创新的纳米平台用于PD治疗，显示出血脑屏障穿透能力，并在神经炎症部位精确积累。这种靶向递送能够实现比现有治疗方式更精确、更有效的治疗。
在体外和体内评估了DCM@Nar-NCs的血脑屏障穿透效率和脑靶向递送。在细胞和动物水平上全面研究了其神经保护作用。最后，在1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的PD小鼠模型中验证了DCM@Nar-NCs改善运动功能障碍和认知障碍的能力。
DCM@Nar-NCs表现出显著增强的血脑屏障通透性，并能发挥双重治疗作用。值得注意的是，DCM@Nar-NCs调节小胶质细胞极化（从促炎M1表型转变为神经保护M2表型），从而减轻神经炎症级联反应。此外，DCM@Nar-NCs可以改善线粒体功能障碍，从而防止多巴胺能神经元的凋亡和破坏。最后，动物模型中的行为评估证实了DCM@Nar-NCs具有显著的逆转PD相关运动缺陷和认知障碍的能力。
总体而言，本研究中开发的新型PD治疗方法具有卓越的生物安全性和治疗效果，突出了其在临床转化方面的强大潜力。
