Sabu Arjun, Huang Yu Ching, Sharmila Ramalingam, Sun Chih-Yuan, Shen Min-Ying, Chiu Hsin-Cheng
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu City, Taiwan.
Department of Neurology, Taoyuan General Hospital, Ministry of Health and Welfare, Taiwan.
Mater Today Bio. 2024 Aug 27;28:101213. doi: 10.1016/j.mtbio.2024.101213. eCollection 2024 Oct.
An increasing number of medications have been explored to treat the progressive and irreversible Alzheimer's disease (AD) that stands as the predominant form of dementia among neurodegenerative ailments. However, assertions about toxic side effects of these drugs are a significant hurdle to overcome, calling for drug-free nanotherapeutics. Herein, a new therapeutic strategy devoid of conventional drugs or other cytotoxic species was developed. The constructed superparamagnetic iron oxide nanoparticles (SPIONs) nanospinners can accrete neurotoxic β-amyloid 42 oligomers (oAβ) into aggregated magnetic plaques (mpAβ) by mechanical rotating force via remote interaction between nanoparticles and the applied magnetic field. While the cellular uptake of mpAβ attained from the magnetic stirring treatment by neuronal cells is severely limited, the facile phagocytic uptake of mpAβ by microglial cells leads to the polarization of the brain macrophages to M2 phenotype and thus the increased anti-inflammatory responses to the treatment. The SPION stirring treatment protects the AD mice from memory deterioration and maintain cognitive ability as evidenced from both nesting and Barnes maze tests. The examination of the oAβ injected brain tissues with the stirring treatment showed significant amelioration of functional impairment of neurons, microglia, astrocytes and oligodendrocytes alongside no obvious tissue damage caused by stirring meanwhile complete degradation of SPION was observed at day 7 after the treatment. The in vitro and animal data of this work strongly corroborate that this new modality of undruggable stirring treatment with SPIONs provides a new feasible strategy for developing novel AD treatments.
越来越多的药物被用于治疗进行性且不可逆的阿尔茨海默病(AD),它是神经退行性疾病中痴呆的主要形式。然而,关于这些药物毒性副作用的说法是需要克服的重大障碍,因此需要无药物的纳米疗法。在此,我们开发了一种不含传统药物或其他细胞毒性物质的新治疗策略。构建的超顺磁性氧化铁纳米颗粒(SPIONs)纳米旋转器可以通过纳米颗粒与外加磁场之间的远程相互作用,利用机械旋转力将神经毒性β-淀粉样蛋白42寡聚体(oAβ)聚合成聚集的磁性斑块(mpAβ)。虽然神经元细胞通过磁力搅拌处理获得的mpAβ的细胞摄取受到严重限制,但小胶质细胞对mpAβ的易吞噬摄取会导致脑巨噬细胞向M2表型极化,从而增强治疗的抗炎反应。SPION搅拌处理可保护AD小鼠免于记忆衰退并维持认知能力,这在筑巢和巴恩斯迷宫测试中均得到证实。对经搅拌处理后注射oAβ的脑组织进行检查发现,神经元、小胶质细胞、星形胶质细胞和少突胶质细胞的功能损伤有显著改善,同时搅拌未造成明显组织损伤,并且在治疗后第7天观察到SPION完全降解。这项工作的体外和动物实验数据有力地证实,这种用SPION进行不可药物化搅拌处理的新模式为开发新型AD治疗方法提供了一种新的可行策略。
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