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

Abstract

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.