Magneto-aerotactic bacteria deliver drug-containing nanoliposomes to tumour hypoxic regions

Oxygen depleted hypoxic regions in the tumour are generally resistant to therapies(1). Although nanocarriers have been used to deliver drugs, the targeting ratios have been very low. Here, we show that the magneto-aerotactic migration behaviour(2) of magnetotactic bacteria(3), Magnetococcus marinus strain MC-1(4), can be used to transport drug-loaded nanoliposomes into hypoxic regions of the tumour. In their natural environment, MC-1 cells, each containing a chain of magnetic iron-oxide nanocrystals(5), tend to swim along local magnetic field lines and towards low oxygen concentrations(6) based on a two-state aerotactic sensing system(2). We show that when MC-1 cells bearing covalently bound drug-containing nanoliposomes were injected near the tumour in SCID Beige mice and magnetically guided, up to 55% of MC-1 cells penetrated into hypoxic regions of HCT116 colorectal xenografts. Approximately 70 drug-loaded nanoliposomes were attached to each MC-1 cell. Our results suggest that harnessing swarms of microorganisms exhibiting magneto-aerotactic behaviour can significantly improve the therapeutic index of various nanocarriers in tumour hypoxic regions.