Self-navigated NIR-II thermophoretic liposome nanomotors for directed tumor delivery and enhanced chemotherapy

Nanomotors are appealing drug carriers with deep tissue penetration to overcome biological barriers. Though high motion efficiency has been achieved with NIR-II light driven nanomotors, insufficient directional control and material biocompatibility limit their broad application. Herein, leveraging commercially available liposomal doxorubicin (DOX) as a platform, we develop a magnetic-steering NIR-II light thermophoretic liposomal nanomotor (LipNM) by asymmetrically incorporating magnetic photothermal Fe 3 O 4 @Cu 9 S 8 nanoparticles into the lipid bilayer, firstly realizing directional nanoscale self-thermophoresis. The embedded Fe 3 O 4 @Cu 9 S 8 nanoparticles respond to a brief magnet stimulation for spatiotemporal steering and NIR-II irradiation with local temperature increase for self-thermophoresis of LipNMs, which further facilitate tumor tissue targeting and deep tumor penetration, respectively. The direction-controllable thermophoretic LipNMs demonstrate good biocompatibility and increase the delivery efficiency of DOX by 186% compared to passive liposomal doxorubicin. Owing to the targeted accumulation and deep tissue penetration at the tumor site, the therapeutic efficiency of LipNMs for breast cancer in vivo is as high as 94.9%, providing a promising strategy for cancer therapy. • A novel NIR-II thermophoretic liposome nanomotor (LipNM) with active navigation is constructed via asymmetric ultrasmall inorganic nanoparticles incorporation into the lipid bilayers of liposomal DOX. • Nanoparticles embedded in LipNMs respond to a brief magnet stimulation for motion directionality and NIR-II irradiation for photothermal propulsion, firstly realizing directional nanoscale self-thermophoresis. • Precisely guided LipNMs exhibit deeper penetration and targeted tumor accumulation, elevating tumor-targeted doxorubicin delivery by ∼186% and achieving a 94.9% therapeutic efficacy in breast cancer.