Light-driven jet-propelled nanomotors for enhanced drug penetration and therapy

Nanomotors endowed with active migration capabilities represent a promising strategy to overcome physical tumor microenvironmental (TME) barriers, thereby enabling deep drug penetration for precise cancer therapy. Nevertheless, their widespread application is still constrained by complex fabrication processes and limited internal loading capacity. Herein, we report a simple and reproducible hard-template layer-by-layer coating approach for the construction of eccentric hollow nanomotors (Au@MONs), which are loaded with low-boiling-point perfluorohexane (PFH) as the propulsion fuel. Under near-infrared irradiation, the Au@MONs@PFH nanomotor efficiently converts light energy into heat, triggering rapid vaporization of the encapsulated PFH. This vaporization process generates gas bubbles that serve as the driving force for nanomotor propulsion. The as-prepared Au@MONs exhibit exceptional photothermal stability and superior propulsion performance. After irradiation, a marked increase in bubble generation, reduced hydrodynamic size, elevated mean-square displacement (MSD), and a directional migration trajectory were observed, collectively confirming efficient light-driven jet propulsion. Furthermore, these light-driven jet-propelled nanomotors effectively enhanced cellular internalization and facilitated deep intratumoral delivery of doxorubicin (DOX), ultimately leading to superior tumor accumulation and therapeutic efficacy <i>in vivo</i>. This work provides a facile platform for constructing multifunctional nanomotors with robust propulsion and therapeutic performance, opening new avenues for advancing precision cancer treatment.