Biological Nanocarrier-Based Therapy for Breast Cancer Using Modified <i>Faecalibaculum rodentium</i> -Derived Bacterial Membrane Vesicles

The traditional treatment of triple-negative breast cancer (TNBC) still has limitations. Bacterial membrane vesicles (MVs), as a type of natural nanocarrier, have emerged as a focal point of research in the field of cancer therapy due to their convenient modification essence, biodegradability, and immune regulatory functions. A strategy was proposed to modify MVs loaded with apatinib using αPD-L1 as a target to enhance the accumulation at triple-negative breast cancer sites while leveraging the intrinsic characteristics of MVs to improve the suppressive tumor immune microenvironment (TIME). It focused on the preparation, modification, characterization, and safety evaluation of bacterial vesicles, as well as functional evaluation of modified MVs, and their application in antitumor therapy, particularly their potential regulation effects on TIME in a breast cancer mouse model. Initially, we observed that the expression level of a type of probiotic, called Faecalibaculum rodentium, in mouse breast cancer tissues was lower than in the corresponding adjacent tissues. Subsequently, we characterized the empty vesicles of F. R to ensure their physical and chemical stability, followed by a series of safety tests confirming their low toxicity and good biocompatibility. We then assessed the effects of the modified vesicles on cancer cells in vitro, which demonstrated significant anticancer effects, particularly in inhibiting the epithelial-mesenchymal transition, angiogenesis, and promoting apoptosis. In vivo studies showed that the modified vesicles, MVs/Apatinib/aPD-L1, exhibited excellent anticancer effects across three animal models by improving TIME. This study provided the possibility of an efficient and low toxicity nanodrug carrier platform.