Piezoelectric catalytic activation of cGAS-STING pathway by Ga-based liquid metal nanoparticles for enhanced antitumor immunotherapy.

Abstract

The abnormal vascular structure and impaired lymphatic drainage in tumor tissue lead to interstitial fluid accumulation, resulting in elevated interstitial fluid pressure, which severely hinders the intratumoral penetration of therapeutic drugs. Liquid metals (LM), with their unique dynamic atomic rearrangement, high electrical conductivity, and remarkable deformability, exhibit superior catalytic efficiency and penetrability unattainable by conventional catalytic therapies. Herein, we innovatively constructed a biomimetic nanocatalytic system (LM@M) based on Ga₆₇In_20.5Sn_12.5 coated with tumor cytomembranes. Under ultrasound stimulation, LM@M piezocatalytically decomposes interstitial water in tumors to generate hydrogen, significantly reducing tumor interstitial pressure while simultaneously activating the cGAS-STING immune pathway to enhance antigen presentation and promote T-cell infiltration into deep tumor regions. Experimental results demonstrate that LM@M not only markedly improves drug penetration efficiency in tumor tissues but also induces a robust and sustained antitumor immune response, successfully eliminating both primary and distal metastatic tumors in tumor-bearing mice. This study innovatively integrates the catalytic properties of liquid metals with immunomodulation, unveiling the dynamic deformation behavior of LM-based nanomedicines within the tumor microenvironment, thereby providing a novel strategy for their biomedical applications.