Boosting Cancer Chemotherapy through Targeted <i>Akkermansia muciniphila</i> Modulation by Tumor-Repopulating Cell-Derived Microparticles

The complex relationship between gut microbiota and cancer therapy has received extensive attention, proposing gut microbiota modulation as a promising strategy for enhancing anticancer efficacy. In this work, tumor-repopulating cell-derived microparticles (3D-MPs) encapsulated with doxorubicin (DOX) are developed to improve cancer treatment outcomes through targeted interaction with gut microbiota, particularly <i>Akkermansia muciniphila</i> (AKK). This delivery system efficiently accumulates in the intestines via the integrin α5-fibronectin pathway, promoting AKK abundance through the pro-proliferative effects of 3D-MPs on AKK and the inhibitory action of DOX on competing gut bacteria, such as <i>Helicobacter</i> and <i>Prevotella</i>, for improved anticancer effects. Our findings demonstrate the potential of leveraging gut microbiota modulation to optimize therapeutic outcomes in cancer treatments, offering a novel approach to synergistic cancer therapy.