Engineered probiotic-propelled micro-robot as biological truck for deep tumor penetration and treatment.

Effectively penetrating complex tumor physiological barriers and delivering therapeutic drugs precisely to each cancer cell remains a key challenge in modern oncology. For this purpose, we have developed an engineered probiotic-driven, macrophage membrane-camouflaged microrobot (EcN-MP/DOX). This system can not only serve as a "biological truck" for precise delivery of anti-cancer drugs, but also a natural immunomodulatory agent. By coating the surface of EcN with hybrid vesicles composed of macrophage membranes and pH-responsive liposomes, this system ingeniously integrates the autonomous motility and hypoxia chemotaxis of probiotics, the active targeting capability of macrophage membranes, and the pH-triggered drug release property. This design enables precise infiltration into and drug enrichment within deep tumor tissues. Furthermore, EcN-MP/DOX can express tumor-specific antigens and function as an "in situ vaccine" by promoting the secretion of IFN-γ and TNF-α, thereby stimulating a potent anti-tumor T cell immune response. Consequently, this microrobot achieves synergistic chemotherapy and immunotherapy. Experimental results demonstrate that EcN-MP/DOX exhibits outstanding tissue penetration and antitumor efficacy in human-derived tumor organoids constructed in vitro, as well as promising therapeutic effects in vivo. Moreover, this drug delivery system shows excellent biocompatibility and safety, offering a promising preclinical strategy that merits further translational investigation.