Ashkarran Ali Akbar, Tadjiki Soheyl, Lin Zijin, Hilsen Kylie, Ghazali Noor, Krikor Sarah, Sharifi Shahriar, Asgari Meisam, Hotchkin Michael, Dorfman Adam, Ho Karen S, Mahmoudi Morteza
Department of Radiology and Precision Health Program, Michigan State University, East Lansing, Michigan 48824, United States.
Postnova Analytics Inc., Salt Lake City, Utah 84102, United States.
ACS Pharmacol Transl Sci. 2024 Mar 14;7(4):1169-1177. doi: 10.1021/acsptsci.4c00028. eCollection 2024 Apr 12.
The interaction between nanoparticles (NPs) and biological environments is profoundly influenced by a stable, strongly adsorbed "hard" protein corona. This corona significantly determines the NPs' pharmacokinetics and biological destiny. Our study delves into the mechanisms by which colloidal Au nanocrystals that are synthesized electrochemically without surface-capping organic ligands, known as CNM-Au8, traverse the blood-brain barrier (BBB) and target human brain tissue for treating neurodegenerative disorders. We discovered that upon interaction with human plasma, CNM-Au8 gold nanocrystals (AuNCs) effectively attract a variety of crucial apolipoproteins, notably apolipoproteins E, to their surfaces. This interaction likely facilitates their passage through the BBB. Furthermore, the coronas of these AuNCs exhibit a substantial presence of albumin and a notable absence of opsonin-based proteins, contributing to prolonged blood circulation. These characteristics align well with the clinical performance observed for the CNM-Au8 NCs. This study highlights that AuNCs with intentionally engineered structures and surfactant-free surfaces can create a distinct protein corona composition. This finding holds significant promise for the development of advanced therapeutic agents aimed at combating neurodegenerative diseases.
纳米颗粒(NPs)与生物环境之间的相互作用受到稳定的、强烈吸附的“硬”蛋白冠的深刻影响。这种蛋白冠显著决定了纳米颗粒的药代动力学和生物学命运。我们的研究深入探讨了通过电化学合成的无表面封端有机配体的胶体金纳米晶体(称为CNM-Au8)穿越血脑屏障(BBB)并靶向人类脑组织以治疗神经退行性疾病的机制。我们发现,与人类血浆相互作用时,CNM-Au8金纳米晶体(AuNCs)有效地将多种关键载脂蛋白,特别是载脂蛋白E吸引到其表面。这种相互作用可能促进它们通过血脑屏障。此外,这些AuNCs的蛋白冠显示出大量白蛋白的存在,且基于调理素的蛋白明显缺乏,这有助于延长血液循环。这些特性与观察到的CNM-Au8纳米晶体的临床性能非常吻合。这项研究强调,具有特意设计结构和无表面活性剂表面的AuNCs可以形成独特的蛋白冠组成。这一发现对于开发旨在对抗神经退行性疾病的先进治疗药物具有重大前景。