What question did this study set out to answer?

This research aims to design a gliding nanomachine that delivers chloroquine and nanodiamond to enhance tumor cell death by regulating autophagy and ferroptosis.

March 16, 2026Open Access

Proactive gliding-nanomachines declined tumor autophagy for enhanced tumor death

Key Points

This research aims to design a gliding nanomachine that delivers chloroquine and nanodiamond to enhance tumor cell death by regulating autophagy and ferroptosis.
Created biocompatible gliding nanomachines (Fe@L-arg@CQ/ND@HA) for drug delivery.
Utilized Fenton-reaction to release reactive oxygen species (ROS).
Examined effects of NO release on tumor autophagy and ferroptosis in vitro.
Assessed the movement of nanomachines in response to ROS stimulation.
Nanomachines effectively declined tumor autophagy when combined with chloroquine and nanodiamond.
Enhanced ferroptosis was observed, leading to increased tumor cell death.
NO release facilitated the active gliding of nanomachines.
Polyamine output was significantly elevated, amplifying the tumor treatment effect.

Abstract

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.

Proactive gliding-nanomachines declined tumor autophagy for enhanced tumor death

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Abstract

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