Cheng Guowang, Liu Zhiwen, Yan Zhao, Wu Jiaxin, Li Zilin, Gao Sijia, Zheng Chunye, Guo Shuanshuan, Pan Yue, Chen Xiaojia, Lin Guanghui, Zhou Jianhua, Chen Tongkai
School of Pharmaceutical Sciences, Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China; School of Life Sciences and Biopharmaceutics, Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
J Control Release. 2025 Jan 10;377:591-605. doi: 10.1016/j.jconrel.2024.11.066. Epub 2024 Nov 29.
Parkinson's disease (PD)-induced motor dysfunction and cognitive impairment are becoming increasingly common due to global population aging. However, efficient treatment strategies for these conditions are still lacking. Recent studies indicated that neuroinflammation and neuronal apoptosis could greatly worsen the symptoms of PD. Therefore, anti-apoptotic and anti-inflammatory drugs could be useful in the management of PD. In the present study, minocycline (MIN)-loaded FeO nanoparticles (FeO-MIN NPs) were prepared for the targeted treatment of PD. Owing to their near-infrared (NIR) irradiation-induced photothermal effects, the FeO-MIN NPs could cross the blood-brain barrier (BBB), thus enhancing the delivery of FeO-MIN NPs to the brain parenchyma. Subsequently, the FeO-MIN NPs exerted strong anti-inflammatory effects and alleviated neuroinflammation in the brain. Furthermore, they exerted anti-oxidative effects, scavenging excessive reactive oxygen species in the brain parenchyma and thus protecting both dopaminergic and hippocampal neurons from neuroinflammation and apoptosis. Consequently, FeO-MIN NPs + NIR treatment attenuated the motor dysfunction and cognitive impairment observed in PD mice. Notably, the FeO-MIN NPs also showed high biocompatibility. Hence, these BBB-penetrating MIN-loaded FeO NPs demonstrate great therapeutic potential for PD accompanied by cognitive impairment.
由于全球人口老龄化，帕金森病（PD）引起的运动功能障碍和认知障碍正变得越来越普遍。然而，针对这些病症的有效治疗策略仍然缺乏。最近的研究表明，神经炎症和神经元凋亡会大大加重PD的症状。因此，抗凋亡和抗炎药物可能有助于PD的治疗。在本研究中，制备了负载米诺环素（MIN）的FeO纳米颗粒（FeO-MIN NPs）用于PD的靶向治疗。由于其近红外（NIR）辐射诱导的光热效应，FeO-MIN NPs可以穿过血脑屏障（BBB），从而增强FeO-MIN NPs向脑实质的递送。随后，FeO-MIN NPs发挥了强大的抗炎作用，减轻了脑中的神经炎症。此外，它们还发挥了抗氧化作用，清除脑实质中过量的活性氧，从而保护多巴胺能神经元和海马神经元免受神经炎症和凋亡的影响。因此，FeO-MIN NPs + NIR治疗减轻了PD小鼠中观察到的运动功能障碍和认知障碍。值得注意的是，FeO-MIN NPs还表现出高生物相容性。因此，这些可穿透BBB的负载MIN的FeO NPs对伴有认知障碍的PD具有巨大的治疗潜力。
