Genetically engineered bacteria with jacketed biofilm for enhancing drug delivery into tumor

Tumor-targeted bacteria have emerged as promising drug carriers due to their intrinsic motility and hypoxia-homing property. Therapeutic agents can be loaded onto the bacterial surface, enabling their active delivery into tumor tissues. However, premature drug release during systemic circulation-likely triggered by various physiological/physical factors-inevitably results in reduced efficacy or increased off-target toxicity. Here, we present a genetic engineering strategy that enables <i>E. coli</i> MG1655 (EC) to autonomously produce a biofilm "jacket" on its surface (termed MEC) by regulating the expression of the biofilm-associated Csg gene cluster. This biofilm coating markedly enhances drug adsorption (1.7-fold increase for the model drug indocyanine green, ICG) and effectively prevents off-target leakage during systemic circulation. Benefiting from its tumor-homing capability and biofilm-mediated protection, MEC can deliver substantially more ICG into tumor inner regions. In murine tumor models, MEC-mediated delivery achieves significantly enhanced intratumoral drug retention and photothermal efficacy in comparison with the wild-type bacterial carrier. This work demonstrates an effective tumor-targeted drug delivery strategy based on genetically engineered biofilm technology, offering a promising avenue for precision bacterial oncology.