纳米生物材料辅助淀粉样β嵌合抗原受体巨噬细胞(CAR-M)疗法的新进展:减轻阿尔茨海默病中的斑块负担
Emerging advances in nano-biomaterial assisted amyloid beta chimeric antigen receptor macrophages (CAR-M) therapy: reducing plaque burden in Alzheimer's disease.
作者信息
Kushwaha Nishabh, Panjwani Drishti, Patel Shruti, Ahlawat Priyanka, Yadav Mange Ram, Patel Asha S
机构信息
Department of Pharmaceutics, Parul Institute of Pharmacy, Parul University, Vadodara, India.
Research and Development Cell, Parul University, Vadodara, India.
出版信息
J Drug Target. 2025 Feb;33(2):185-205. doi: 10.1080/1061186X.2024.2417012. Epub 2024 Oct 21.
Alzheimer's disease is the most common form, accounting for 60-70% of 55 million dementia cases. Even though the precise pathophysiology of AD is not completely understood, clinical trials focused on antibodies targeting aggregated forms of β amyloid (Aβ) have demonstrated that reducing amyloid plaques can arrest cognitive decline in patients in the early stages of AD. In this study, we provide an overview of current research and innovations for controlled release from nano-biomaterial-assisted chimeric antigen receptor macrophage (CAR-M) therapeutic strategies targeted at AD. Nano-bio materials, such as iron-oxide nanoparticles (IONPs), can be made selectively (Hp-Hb/mannose) to bind and take up Aβ plaques like CAR-M cells. By using nano-bio materials, both the delivery and stability of CAR-M cells in brain tissue can be improved to overcome the barriers of the BBB and enhance therapeutic effects. By enhancing the targeting capabilities and stability of CAR-M cells, mRNA-loaded nano-biomaterials can significantly improve the efficacy of immunotherapy for plaque reduction in AD. This novel strategy holds promise for translating preclinical successes into clinical applications, potentially revolutionising the management of AD.
阿尔茨海默病是最常见的形式,占5500万例痴呆病例的60 - 70%。尽管AD的确切病理生理学尚未完全了解,但针对聚集形式的β淀粉样蛋白(Aβ)的抗体的临床试验表明,减少淀粉样斑块可以阻止AD早期患者的认知衰退。在本研究中,我们概述了当前针对AD的纳米生物材料辅助嵌合抗原受体巨噬细胞(CAR-M)治疗策略的控释研究和创新。纳米生物材料,如氧化铁纳米颗粒(IONPs),可以被选择性地(血红蛋白-血红蛋白/甘露糖)制成像CAR-M细胞一样结合并摄取Aβ斑块。通过使用纳米生物材料,可以提高CAR-M细胞在脑组织中的递送和稳定性,以克服血脑屏障的障碍并增强治疗效果。通过增强CAR-M细胞的靶向能力和稳定性,负载mRNA的纳米生物材料可以显著提高AD中减少斑块的免疫治疗效果。这种新策略有望将临床前的成功转化为临床应用,可能彻底改变AD的治疗管理。