Endosomal escapable cryo-treatment-driven membrane-encapsulated Ga liquid-metal transformer to facilitate intracellular therapy

Abstract

•Freezing drives Ga particles to transform from sphere to cactus-like structure •LM transformers can realize endosomal escape for drug release under freezing •Ga/MPs exhibit significant tumor growth inhibition and prolonged survival time •LM transformers can be applied for high-resolution in vivo CT imaging Metallic shape transformable materials hold big promise for improved intracellular therapy. However, until now, there have been rather limited biomedical practices for such materials, which is mainly attributed to their inherent uncontrolled morphological transformation, non-selective destruction, and difficult metabolization. Here, Ga-based liquid metal is found to exhibit remarkable transformation from sphere shape to cactus-like structure in micro-scale under freezing. Particularly, only cell membrane-encapsulated Ga particles (Ga/MPs) display dramatic shape variation in cooling under cryo-transmission electron microscopy (cryo-TEM). Following that, cryo-triggered Ga/MPs transformers are designed for effective endosomal escape via a physical mechanical strategy to disrupt the endosomal membrane, which leads to highly efficient cancer cell killing. Ga/MPs exhibit significant tumor growth inhibition and prolonged survival time according to the collaborative efficacy of cryoablation and endosomal escape mechanism, as well as high-resolution in vivo computed tomography (CT) imaging. This study opens a versatile strategy based on Ga particle transformer to assist high-performance precise intracellular therapy in future tumor therapeutics. Metallic shape transformable materials hold big promise for improved intracellular therapy. However, until now, there have been rather limited biomedical practices for such materials, which is mainly attributed to their inherent uncontrolled morphological transformation, non-selective destruction, and difficult metabolization. Here, Ga-based liquid metal is found to exhibit remarkable transformation from sphere shape to cactus-like structure in micro-scale under freezing. Particularly, only cell membrane-encapsulated Ga particles (Ga/MPs) display dramatic shape variation in cooling under cryo-transmission electron microscopy (cryo-TEM). Following that, cryo-triggered Ga/MPs transformers are designed for effective endosomal escape via a physical mechanical strategy to disrupt the endosomal membrane, which leads to highly efficient cancer cell killing. Ga/MPs exhibit significant tumor growth inhibition and prolonged survival time according to the collaborative efficacy of cryoablation and endosomal escape mechanism, as well as high-resolution in vivo computed tomography (CT) imaging. This study opens a versatile strategy based on Ga particle transformer to assist high-performance precise intracellular therapy in future tumor therapeutics.