Bacterial hitchhiking with drug-loaded nanoparticles as a drug delivery strategy for cancer immunotherapy

Abstract Select strains of bacteria show significant therapeutic promise in oncology, but there are major limitations for their clinical implementation, including their fast clearance from the circulation and dose-limiting toxicity. To address this challenge, we propose delivering bacteria alongside drug-loaded nanoparticles to reduce the premature clearance of bacteria from the circulation and improve their therapeutic efficacy. We evaluated the ability of the bacterium Magnetospirillum gryphiswaldense, an environmental isolate that holds promise as an anti-cancer immunotherapy, to carry drug-loaded nanoliposomes into melanoma tumors. Using the B16F10 melanoma mouse model, we demonstrated that when injected locally, the bacteria can significantly reduce tumor growth while inducing a strong immune response. Further, we showed that drug-loaded nanoliposomes can be conjugated to the surface of bacteria improving their tumoral delivery and yielding a stronger anticancer response when delivered systemically. These results suggest that bacterial hitchhiking is a promising systemic drug delivery strategy for cancer immunotherapy.