Ga(III) ion release from gallium-based liquid metals: The trade-off between efficacy and safety

Due to unique pharmacological activities and distinctive physicochemical properties, gallium-based liquid metals (LMs) have attracted tremendous attention in therapeutics. As biodegradable metallic materials, gallium-based LMs can predominantly release Ga(III) ions under physiological conditions, which represents a double-edged sword for clinical translation. On the one hand, the Ga(III) ions act as redox-inert Fe(III) competitive inhibitors and may provide therapeutic effects for broad-spectrum therapeutic applications. On the other hand, upon nonspecific biodistribution or uncontrolled Ga(III) release, substitution of Fe(III) by Ga(III) may disturb iron metabolism in normal cells and subsequently induce toxicological outcomes. Therefore, understanding and managing the trade-off between efficacy and safety is a key prerequisite for the clinical translation of gallium-based LMs. This review aims to systematically summarize the therapeutic activities and toxicological characteristics of gallium-based LMs. Meaningfully, the unresolved challenges and future perspectives regarding the balance between efficacy and safety are outlined to inspire future academic explorations and clinical translation.