title: Magneto-aerotactic bacteria deliver drug-containing nanoliposomes to tumour hypoxic regions.
abstract: Oxygen-depleted hypoxic regions in the tumour are generally resistant to therapies. Although nanocarriers have been used to deliver drugs, the targeting ratios have been very low. Here, we show that the magneto-aerotactic migration behaviour of magnetotactic bacteria, 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 nanocrystals, tend to swim along local magnetic field lines and towards low oxygen concentrations based on a two-state aerotactic sensing system. 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.
authors.affiliation: NanoRobotics Laboratory, Department of Computer and Software Engineering, Institute of Biomedical Engingeering, Polytechnique Montréal, Montréal H3T 1J4, Canada.
authors.forename: Ouajdi
authors.initials: O
authors.lastname: Felfoul
authors.affiliation: NanoRobotics Laboratory, Department of Computer and Software Engineering, Institute of Biomedical Engingeering, Polytechnique Montréal, Montréal H3T 1J4, Canada.
authors.forename: Mahmood
authors.initials: M
authors.lastname: Mohammadi
authors.affiliation: NanoRobotics Laboratory, Department of Computer and Software Engineering, Institute of Biomedical Engingeering, Polytechnique Montréal, Montréal H3T 1J4, Canada.|Department of Biomedical Engineering, McGill University, Montréal H3A 2B4, Canada.
authors.forename: Samira
authors.initials: S
authors.lastname: Taherkhani
authors.affiliation: NanoRobotics Laboratory, Department of Computer and Software Engineering, Institute of Biomedical Engingeering, Polytechnique Montréal, Montréal H3T 1J4, Canada.
authors.forename: Dominic
authors.initials: D
authors.lastname: de Lanauze
authors.affiliation: McGill University Health Centre, Montréal H4A 3J1, Canada.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhong Xu
authors.affiliation: NanoRobotics Laboratory, Department of Computer and Software Engineering, Institute of Biomedical Engingeering, Polytechnique Montréal, Montréal H3T 1J4, Canada.
authors.forename: Dumitru
authors.initials: D
authors.lastname: Loghin
authors.affiliation: Department of Biomedical Engineering, McGill University, Montréal H3A 2B4, Canada.|Department of Chemistry, University of Montréal (UdM), Montréal H3C 3J7, Canada.
authors.forename: Sherief
authors.initials: S
authors.lastname: Essa
authors.affiliation: McGill University Health Centre, Montréal H4A 3J1, Canada.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Jancik
authors.affiliation: McGill University Health Centre, Montréal H4A 3J1, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Houle
authors.affiliation: Department of Chemistry, University of Montréal (UdM), Montréal H3C 3J7, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: Lafleur
authors.affiliation: Department of Pathology and Cell Biology, Institute for Research in Immunology and Cancer (IRIC), University of Montréal, Montréal H3T 1J4, Canada.
authors.forename: Louis
authors.initials: L
authors.lastname: Gaboury
authors.affiliation: Department of Biomedical Engineering, McGill University, Montréal H3A 2B4, Canada.|Faculty of Dentistry, McGill University, Montréal H3A 1G1, Canada.
authors.forename: Maryam
authors.initials: M
authors.lastname: Tabrizian
authors.affiliation: NanoRobotics Laboratory, Department of Computer and Software Engineering, Institute of Biomedical Engingeering, Polytechnique Montréal, Montréal H3T 1J4, Canada.
authors.forename: Neila
authors.initials: N
authors.lastname: Kaou
authors.affiliation: NanoRobotics Laboratory, Department of Computer and Software Engineering, Institute of Biomedical Engingeering, Polytechnique Montréal, Montréal H3T 1J4, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Atkin
authors.affiliation: Department of Oncology, Segal Cancer Centre, Jewish General Hospital, McGill University, Montréal H3T 1E2, Canada.
authors.forename: Té
authors.initials: T
authors.lastname: Vuong
authors.affiliation: Department of Oncology, Segal Cancer Centre, Jewish General Hospital, McGill University, Montréal H3T 1E2, Canada.
authors.forename: Gerald
authors.initials: G
authors.lastname: Batist
authors.affiliation: Departments of Biochemistry, Medicine and Oncology, Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montréal H3A 1A3, Canada.
authors.forename: Nicole
authors.initials: N
authors.lastname: Beauchemin
authors.affiliation: McGill University Health Centre, Montréal H4A 3J1, Canada.
authors.forename: Danuta
authors.initials: D
authors.lastname: Radzioch
authors.affiliation: NanoRobotics Laboratory, Department of Computer and Software Engineering, Institute of Biomedical Engingeering, Polytechnique Montréal, Montréal H3T 1J4, Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Martel
mesh_terms: D020561:Alphaproteobacteria; D000818:Animals; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016503:Drug Delivery Systems / Q000379:methods*; D005290:Ferric Compounds / Q000737:chemistry / Q000494:pharmacology; D045325:HCT116 Cells; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D060526:Magnetic Fields; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D023041:Xenograft Model Antitumor Assays
chemical_list: D005290:Ferric Compounds; C000499:ferric oxide