Near-Infrared Light-Powered Janus Nanomotor Significantly Facilitates Inhibition of Amyloid-β Fibrillogenesis

Inspired by the natural motors, artificial nanomotors (NMs) have emerged as intelligent, advanced, and multifunctional nanoplatforms that can perform complex tasks in living environments. However, the functionalization of these fantastic materials is in its infancy, hindering the success of this booming field. Herein, an inhibitor-conjugated near-infrared (NIR) laser-propelled Janus nanomotor (JNM-I) was constructed and first applied in the modulation of amyloid-β protein (Aβ) aggregation which is highly associated with Alzheimer's disease (AD). Under NIR light illumination, JNM-I exhibited efficient propulsion through the "self-thermophoresis" effect, and the active motion of JNM-I increased the opportunity of the contacts between the immobilized inhibitors and Aβ species, leading to an intensification of JNM-I on modulating the on-pathway Aβ aggregation, as evidenced by the distinct changes of the amyloid morphology, conformation, and cytotoxicity. For example, with a NIR irradiation, 200 μg/mL of JNM-I increased the cultured SH-SY5Y cell viability from 68% to nearly 100%, but it only protected the cells to 89% viability without an NIR irradiation. Meanwhile, the NIR irradiation effectively improved the blood–brain barrier (BBB) penetration of JNM-I. Such a JNM-I has connected artificial nanomotors with protein aggregation and provided new insight into the potential applications of various nanomotors in the prevention and treatment of AD.