Ultrasoft hydrogel immune millirobot with multimodal locomotion

Abstract

Advancements in cellular immunotherapy demanded efficient immune cell delivery. To meet this need, we introduced hydrogel-based immune millirobots designed for high immune cell loading and precise tumor targeting. These ultrasoft robots, embedded with magnetic nanoparticles, exhibited adaptable locomotion: walking, rolling, climbing, and undulating, enabling navigation through complex biological environments and alignment with varied tumor morphologies. They responded to magnetic fields and ionic or pH changes, facilitating propulsion, grasping, and localized delivery. In vitro, the millirobots eradicated three-dimensional tumor models in four days; in vivo, they notably reduced tumor growth in HepG2-luc tumor-bearing nude mice within 15 days. Bioluminescence imaging confirmed enhanced natural killer cell activity at tumor sites. The robots demonstrated excellent biocompatibility and biodegradability and caused no adverse effects postimplantation. This work showcased a responsive, soft robotic system with potential for advancing immune cell delivery and exploring tumor-immune dynamics in cancer therapy.