Endosomal Escapable Cryo-Treatment Driven Membrane Encapsulated Ga Liquid-Metal Transformer to Facilitate Intracellular Therapy

Metallic/nonmetallic shape transformable materials hold big promise for improved intracellular therapy with efficient endosomal escape in tumor treatments. However, until now, there are still rather limited biomedical practices for such materials which are mainly attributed to their inherent uncontrolled morphological transformation, difficult metabolization, accumulated toxicity, non-selective destruction and difficult real-time imaging. In this study, Ga-based liquid metal, with distinct properties of high thermal conductivity, excellent phase transition, injectability, targetability, easy-preparation and biosafety, is found to exhibit remarkable transformation from sphere shape to cactus-like structure in micro-scale under freezing. Particularly, it is revealed that only cell membrane-encapsulated Ga particles (Ga/MPs) display dramatic shape variation in cooling under Cryo-TEM contrasting to pure Ga particles (GaPs). Following that, the cryo-triggered Ga/MPs transformers are designed for effective endosomal escape via physical-mechanical strategy to disrupt endosomal membrane which lead to highly efficient cancer cell killing. Moreover, under in vivo antitumor treatments settings, Ga/MPs exhibit significant tumor growth inhibition and prolonged survival time to evaluate the collaborative efficacy of cryoablation and endosomal escape mechanism, as well high-resolution in vivo CT imaging is achieved. This study opens a favorable and versatile strategy based on Ga particle transformer to assist high-performance precise intracellular therapy in future tumor therapeutics.