Wang Wenqian, Hassan Md Musfizur, Kapoor-Kaushik Natasha, Livni Lital, Musrie Benjamin, Tang Jianbo, Mahmud Zaheri, Lai Saluo, Wich Peter Richard, Ananthanarayanan Vaishnavi, Moalem-Taylor Gila, Mao Guangzhao
School of Chemical Engineering, University of New South Wales (UNSW Sydney), Sydney, NSW, 2052, Australia.
Electron Microscopy Unit, University of New South Wales (UNSW), Sydney, NSW, 2052, Australia.
Small. 2024 Sep;20(39):e2311921. doi: 10.1002/smll.202311921. Epub 2024 Apr 22.
Neural tracing proteins like horseradish peroxidase-conjugated wheat germ agglutinin (WGA-HRP) can target the central nervous system (CNS) through anatomic retrograde transport without crossing the blood-brain barrier (BBB). Conjugating WGA-HRP to nanoparticles may enable the creation of BBB-bypassing nanomedicine. Microfluidics and two-photon confocal microscopy is applied to screen nanocarriers for transport efficacy and gain mechanistic insights into their interactions with neurons. Protein modification of gold nanoparticles alters their cellular uptake at the axonal terminal and activates fast retrograde transport. Trajectory analysis of individual endosomes carrying the nanoparticles reveals a run-and-pause pattern along the axon with endosomes carrying WGA-HRP-conjugated gold nanoparticles exhibiting longer run duration and faster instantaneous velocity than those carrying nonconjugated nanoparticles. The results offer a mechanistic explanation of the different axonal transport dynamics as well as a cell-based functional assay of neuron-targeted nanoparticles with the goal of developing BBB-bypassing nanomedicine for the treatment of nervous system disorders.
像辣根过氧化物酶共轭麦胚凝集素（WGA-HRP）这样的神经追踪蛋白可以通过解剖学逆行运输靶向中枢神经系统（CNS），而不会穿过血脑屏障（BBB）。将WGA-HRP与纳米颗粒结合可能有助于创建绕过血脑屏障的纳米药物。微流控技术和双光子共聚焦显微镜被用于筛选纳米载体的运输效率，并深入了解它们与神经元相互作用的机制。金纳米颗粒的蛋白质修饰改变了它们在轴突末端的细胞摄取，并激活了快速逆行运输。对携带纳米颗粒的单个内体的轨迹分析揭示了沿轴突的“运行-暂停”模式，携带WGA-HRP共轭金纳米颗粒的内体比携带未共轭纳米颗粒的内体表现出更长的运行持续时间和更快的瞬时速度。这些结果为不同的轴突运输动力学提供了机制解释，并为神经元靶向纳米颗粒提供了基于细胞的功能测定方法，目标是开发用于治疗神经系统疾病的绕过血脑屏障的纳米药物。
