Autophagy‐Mediated Suppression of Tumor Growth by Food‐Grade Lipid Nanoparticles in Mice

Abstract Food‐grade lipid nanoparticles (FLNs) have been widely used as functional carriers of various nutrients and clinical drugs; however, the potential for FLNs to induce substantial biological effects is often overlooked. Here, it is found that FLNs are first delivered to the early endosomes and then preferentially fused with lipid droplets (LDs) after entering the cells through endocytosis. This process leads to a notable LDs accumulation, which in turn triggers autophagy via the AMPK‐mTOR‐ULK1 signaling pathway. The cascade ultimately promotes tumor cell growth and invasion. However, autophagy inhibition while FLNs treatment counteracts these effects and further causes mitochondria damage, increased reactive oxygen species (ROS) levels, and excessive LDs accumulation, eventually leading to cell apoptosis. This indicates a potential anti‐tumor strategy. The animal tests further demonstrate that intratumoral injection of FLNs together with an autophagy inhibitor (3‐MA) effectively suppresses tumor angiogenesis, proliferation, and metastasis without harming normal cells in mice, confirming a promising and safe anti‐tumor strategy of applying FLNs under autophagy inhibition conditions. The findings represent a substantial step forward in comprehending the biological effects of biomedical carriers.