State Key Laboratory of Digital Medical Engineering, Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering, Hainan University, Haikou, 570228, China.
Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, MoE Key Laboratory for Biomedical Photonics, Huazhong University of Science and Technology, Wuhan, 430074, China.
J Nanobiotechnology. 2024 May 23;22(1):278. doi: 10.1186/s12951-024-02543-z.
Amyloid-β (Aβ) readily misfolds into neurotoxic aggregates, generating high levels of reactive oxygen species (ROS), leading to progressive oxidative damage and ultimately cell death. Therefore, simultaneous inhibition of Aβ aggregation and scavenging of ROS may be a promising therapeutic strategy to alleviate Alzheimer's disease pathology. Based on the previously developed antibody 1F12 that targets all forms of Aβ, we developed an Aβ and ROS dual-targeting nanocomposite using biodegradable mesoporous silica nanoparticles as carriers to load ultra-small cerium oxide nanocrystals (bMSNs@Ce-1F12). By modifying the brain-targeted rabies virus glycoprotein 29 (RVG29-bMSNs@Ce-1F12), this intelligent nanocomposite can efficiently target brain Aβ-rich regions. Combined with peripheral and central nervous system treatments, RVG29-bMSNs@Ce-1F12 can significantly alleviate AD symptoms by inhibiting Aβ misfolding, accelerating Aβ clearance, and scavenging ROS. Furthermore, this synergistic effect of ROS scavenging and Aβ clearance exhibited by this Aβ and ROS dual-targeted strategy also reduced the burden of hyperphosphorylated tau, alleviated glial cell activation, and ultimately improved cognitive function in APP/PS1 mice. Our findings indicate that RVG29-bMSNs@Ce-1F12 is a promising nanodrug that can facilitate multi-target treatment of AD.
淀粉样蛋白-β（Aβ）容易错误折叠成神经毒性聚集体，产生高水平的活性氧（ROS），导致进行性氧化损伤，最终导致细胞死亡。因此，同时抑制 Aβ 聚集和清除 ROS 可能是一种有前途的治疗策略，可以缓解阿尔茨海默病的病理。基于先前开发的靶向所有形式 Aβ 的抗体 1F12，我们使用可生物降解的介孔硅纳米粒子作为载体开发了一种 Aβ 和 ROS 双重靶向纳米复合材料，以负载超小氧化铈纳米晶体（bMSNs@Ce-1F12）。通过修饰靶向大脑的狂犬病病毒糖蛋白 29（RVG29-bMSNs@Ce-1F12），这种智能纳米复合材料可以有效地靶向大脑富含 Aβ 的区域。结合外周和中枢神经系统治疗，RVG29-bMSNs@Ce-1F12 通过抑制 Aβ 错误折叠、加速 Aβ 清除和清除 ROS，显著缓解 AD 症状。此外，这种 Aβ 和 ROS 双重靶向策略表现出的 ROS 清除和 Aβ 清除的协同作用也减轻了过度磷酸化 tau 的负担，减轻了神经胶质细胞的激活，最终改善了 APP/PS1 小鼠的认知功能。我们的研究结果表明，RVG29-bMSNs@Ce-1F12 是一种很有前途的纳米药物，可促进 AD 的多靶点治疗。
