Nanocollision promotes locomotion of dendritic cells for tumor therapy.

Abstract

Mechanical stimuli originating from extracellular matrix have been proved to affect antitumor immunity by regulating dendritic cell (DC) locomotion. However, the immunological consequences of ultrasmall bioparticle-induced nanocollision remain largely an unexplored realm despite its ubiquitous and incessant occurrence within the in vivo milieu. Herein, we disclose that nanocollisions caused by endogenous bioparticles, such as extracellular vesicles, can induce localized membrane deformations. This spatially confined mechanical input activates Piezo1 at collision sites and promotes myosin IIA phosphorylation-mediated F-actin stabilization, enhancing DC intrinsic motility. Subsequent diffusion of Ca²⁺ up-regulates chemotaxis machinery, improving their capacity of tumor microenvironment patrolling and lymph node homing for antitumor immunity. This finding reveals a previously unidentified mechanoimmunological mechanism of immune surveillance. To accelerate the translation of this mechanism into clinical therapeutics, we developed an ultrasound-responsive nanocollision generator using gas-liquid-solid triphase conversion. This system achieves precise nanocollision to augment DC locomotion, promoting antitumor immunity in vivo.