Engineered Probiotics-Based Biohybrid-Driven Tumor Metabolic Remodeling To Boost Tumor Photoimmunotherapy

Abstract

Bioengineered probiotics enable new opportunities to address abnormal cancer metabolism and suppressive immune–environment interactions for improved therapeutic susceptibility. Here, Escherichia coli Nissle 1917 (EcN) was constructed to convert ammonia into l-arginine continuously and was further modified with polydopamine (PDA) to form living biotherapeutic argEcN@P for enhanced colorectal cancer eradication. Benefiting from the movement of EcN, argEcN@P could colonize and penetrate deep in tumors through hypoxia targeting and increase the intratumoral l-arginine concentrations. Upon near-infrared light (NIR) irradiation, heating induced by PDA could ablate tumor cells efficiently and release tumor antigens, which induce immunogenic cell death (ICD). More interestingly, argEcN@P remarkably promotes differentiation into M1-like macrophages in tumor tissues, inhibiting primary, distant tumor growth by inducing potent adaptive antitumor immunity. More importantly, argEcN@P treatment efficiently prevented postoperative tumor recurrence by inducing long-term immune memory. Taken together, this platform based on bioengineered probiotics provides a promising strategy for tumor metabolic reprogramming sensitized photothermal immunotherapy in deep tumors.