Proactive gliding-nanomachines declined tumor autophagy for enhanced tumor death

Autophagy was associated with the pathophysiology of various diseases in vivo , and its own regulation was beneficial for the outcomes of specific diseases. Here, we successfully designed a biocompatible active gliding-nanomachine for delivery of chloroquine (CQ)/nanodiamond (ND) and accelerated tumor cell death associated with amplifying ferroptosis and declining autophagy in vitro . Fe was covered onto one side of the surface of the L-arg@CQ/ND@HA, functioning as a controller for the dominated release of NO by sensitive ROS and Fenton-reaction from the catalyzation between Fe 2+ and H 2 O 2 in vitro . The asymmetrical NO release, which was not only the active-component to decline tumor autophagy in combination with ND/CQ, but also the propellants for the nanomachines. After implementing in tumor cell, the dynamic-sliding of nanomachines could be triggered via ROS and the proactive-gliding further strengthened diffusion of CQ/ND, leading to precise-treatment of tumors through enlarging ferroptosis accompanied by polyamine output and interruption of autophagosome lysosome fusion. The synthetized dynamic sliding-nanomachines, with ROS stimulation of movement behavior and proactive delivery of CQ/ND unlocked huge latent capacity as a potential platform for tumor treatment stemed from ferroptosis amplification loop induced polyamine output and declining autophagy in tumor cell. Lin Zhang et al. developed a active gliding - nanomachine (Fe@L-arg@CQ/ND@HA) that could enhance tumor treatment by declining tumor autophagy and amplifying ferroptosis accompanied by polyamine output. These distinctive-nanomachines dramatically accelerated tumor cell death through chloroquine (CQ) synergism nanodiamond (ND). • Fe@L-arg@CQ/ND@HA-nanomachines executed gliding by asymmetric NO release. • Fe 2+ catalyzed H 2 O 2 to produce •OH via Fenton-reaction. • Fe 3+ overload mediated polyamine output to amplify ferroptosis. • Released NO restrained tumor autophagy in combination with CQ/ND.