Modular Biosurface Engineering of Magnetotactic Bacteria for Multimodal Synergistic Cancer Therapy

Bacterial-mediated cancer therapy shows therapeutic potential yet remains constrained by bioavailability and biosafety challenges. We introduce a scalable, modular biosurface-engineering platform for functionalizing wild-type magnetotactic bacteria (Magnetospirillum magneticum, AMB-1), enabling the integration of diverse materials, including small molecules, polymers, nanoparticles, and metal-organic frameworks. As a proof-of-concept, AMB-1@Fe³⁺-PDA (poly dopamine) exemplifies a bacteria-mediated therapeutic strategy that merges tumor-targeted delivery, immunosuppressive tumor microenvironment (TME) reprogramming, and innate immune activation with photothermal-chemodynamic therapy. The Fe³⁺-PDA coating counteracts deep-tissue immunosuppression and primes adaptive immunity, while AMB-1 enhances penetration into resistant TME niches. These mechanisms synergistically suppress aggressive 4T1 breast tumor progression, metastasis, and recurrence while establishing immunological memory. In murine models, two treatment cycles prolonged median survival from 45 to 67 days and elicited systemic antitumor immunity, including abscopal effects targeting untreated distant tumors. This platform establishes a bridge between materials science and synthetic biology, providing a generalizable blueprint for advancing the clinical translation of engineered bacterial therapies.