Bacterial-adjuvant liquid metal nanocomposites for synergistic photothermal immunotherapy

Abstract Gallium-based liquid metals (LMs) have recently attracted attention as next-generation photothermal agents for cancer therapy. However, their clinical application remains limited due to intrinsic instability and poor aqueous dispersibility, which hinder effective tumor accumulation and therapeutic performance. Here, we report the development of biomimetic Lactococcus -functionalized LM nanocomposites (Lacto–LM) that overcome these limitations. Leveraging components derived from the intratumoral probiotic bacterium Lactococcus sp., the resulting nanocomposites exhibit enhanced cellular uptake, improved tumor localization, and excellent photothermal conversion efficiency. Notably, Lactococcus -derived constituents function as intrinsic immune adjuvants, amplifying the antitumor immune response. A single intravenous administration of Lacto–LM followed by just two rounds of near-infrared laser irradiation achieved complete regression of primary tumors. Furthermore, Lacto–LM treatment elicited durable systemic immune memory that suppressed metastasis and prevented tumor recurrence. These findings demonstrate that integrating photothermal therapy with intrinsic immunomodulation via probiotic-functionalized nanocomposites offers a potent and translational strategy for treating refractory cancers. Graphical Abstract