Oxygen depleted hypoxic regions in the tumour are generally resistant to therapies1. Although nanocarriers have been used to deliver drugs, the targeting ratios have been very low. Here, we show that the magneto-aerotactic migration behaviour2 of magnetotactic bacteria3, Magnetococcus marinus strain MC-14, 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 nanocrystals5, tend to swim along local magnetic field lines and towards low oxygen concentrations6 based on a two-state aerotactic sensing system2. 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.
Magnetotactic bacteria MC-1 (MTB) synthesize a chain of magnetic nanoparticles called magnetosomes to navigate in deep-sea environments by orienting themselves in the direction of the Earth's magnetic field. MTB's inherent mobility and ability to be controlled by exposition to an external magnetic field has become of increasing interest for micromanipulation and drug transport applications. In the traditional control schemes, MTB were oriented by exposure to an external magnetic field causing them to align with the magnetic field lines. Directional changes were applied below a critical frequency and, as such, MTB were still able to swim along the generated magnetic field lines. The approach presented here proposes to apply to the MTB an oscillating magnetic field with a frequency beyond a critical limit to in order to exploit the time averaging magnetic field motion behavior of the bacteria cells. Results indicate that a time-multiplexed magnetic field made of various directional cycling fields can control the MTB more efficiently with less power, which is an advantage for future human-scale medical applications.
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