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-1 (ref. 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 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 severe combined immunodeficient 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.
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Taherkhani, S., Mohammadi, M., Daoud, J., Martel, S. & Tabrizian, M.Covalent binding of nanoliposomes to the surface of magnetotactic bacteria acting as self-propelled target delivery agents. ACS Nano8, 5049–5060 (2014).
NanoRobotics Laboratory, Department of Computer and Software Engineering, Institute of Biomedical Engingeering, Polytechnique Montréal, Montréal H3T 1J4, Canada
Dominic de Lanauze,
Michael Atkin &
Department of Biomedical Engineering, McGill University, Montréal H3A 2B4, Canada
Sherief Essa &
McGill University Health Centre, Montréal H4A 3J1, Canada
Yong Zhong Xu,
Daniel Houle &
Department of Chemistry, University of Montréal (UdM), Montréal H3C 3J7, Canada
Sherief Essa &
Department of Pathology and Cell Biology, Institute for Research in Immunology and Cancer (IRIC), University of Montréal, Montréal H3T 1J4, Canada
Faculty of Dentistry, McGill University, Montréal H3A 1G1, Canada
Department of Oncology, Segal Cancer Centre, Jewish General Hospital, McGill University, Montréal H3T 1E2, Canada
Té Vuong &
Departments of Biochemistry, Medicine and Oncology, Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montréal H3A 1A3, Canada
S.M. acted as principal investigator, wrote the paper with assistance from O.F., M.M., D.R., S.T. and N.B. and developed the general principles and methods. G.B. and T.V. provided clinical insights. O.F., M.M., S.T., Y.Z.X., D.d.-L., D.L. and D.H. performed the experiments with tumour-bearing animals. S.J., Y.Z.X. and D.H. carried out the IV injections, processed all blood and tissues for analysis and analysed the samples. L.G. performed immunohistochemistry, immunofluorescence and histopathological evaluations. N.K. and M.M., assisted by M.A., acted as project managers. M.M. and O.F. performed the experiments for the preliminary in vivo proofs of concept. O.F. designed the experimental platform. D.d.-L. tested the magnetotactic control process, which was executed by D.L. M.L. and S.E. synthesized the liposomes. M.T. and S.T. attached the liposomes to the MC-1 cells. M.M. cultivated and prepared the bacteria for injection. M.M., D.R., G.B., L.G., N.B. and S.M. made revisions to the manuscript and figures. Y.Z.X. and D.H. coordinated the implantations of tumour xenografts. D.L. developed and calibrated the MC-1 counting software.
Competing financial interests
The authors declare no competing financial interests.