Self-propelled biohybrids co-deliver oxaliplatin and glucose oxidase for multimodal treatment of colon cancer

As a frontline chemotherapeutic agent for colorectal cancer, oxaliplatin (OXA) exhibits significantly reduced therapeutic efficacy and may induce severe adverse effects, primarily due to limited targeting capacity and impaired drug penetration within the hypoxic tumor microenvironment (TME). To address this challenge, an iron-based metal-organic framework (MOF) was engineered to co-load OXA and glucose oxidase (GOx). This MOF was subsequently immobilized onto the surface of anaerobic Bifidobacterium infantis (Bif). Leveraging the inherent homing capacity of Bif, a self-propelled biohybrid designated MOGP@Bif was developed. Upon accumulation in tumor tissue, the released components synergistically exert: (i) chemodynamic therapy (CDT) via MOF-mediated generation of hydroxyl radicals through enhanced Fenton reactions between Fe²⁺ and endogenous H₂O₂; (ii) chemotherapy via OXA; (iii) starvation therapy via GOx-mediated glucose depletion. Concurrently, glutathione (GSH) depletion enhances oxidative stress, while OXA-mediated hypoxia amelioration further potentiates tumor cell death. MOGP@Bif significantly prolongs the median survival of CT-26 tumor-bearing mice and reduces OXA-related toxic side effects, achieving an approximately fourfold higher intratumoral OXA concentration compared to free OXA treatment. This bacteria-driven platform represents a promising approach for multimodal solid tumor therapy.