Magneto-aerotactic bacteria deliver drug-containing nanoliposomes to tumour hypoxic regions
Ouajdi Felfoul, Mahmood Mohammadi, Samira Taherkhani, Dominic de Lanauze, Yong Zhong Xu, Dumitru Loghin, Sherief Essa, Sylwia Jancik, Daniel Houle, Michel Lafleur, Louis Gaboury, Maryam Tabrizian, Neila Kaou, Michael Atkin, Té Vuong, Gerald Batist, Nicole Beauchemin, Danuta Radzioch, Sylvain Martel, Ouajdi Felfoul, Mahmood Mohammadi, Samira Taherkhani, Dominic de Lanauze, Yong Zhong Xu, Dumitru Loghin, Sherief Essa, Sylwia Jancik, Daniel Houle, Michel Lafleur, Louis Gaboury, Maryam Tabrizian, Neila Kaou, Michael Atkin, Té Vuong, Gerald Batist, Nicole Beauchemin, Danuta Radzioch, Sylvain Martel
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.
Figures
References
- Vaupel P, Mayer A. Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev. 2007;26:225–239.
- Frankel RB, Bazylinski DA, Johnson MS, Taylor BL. Magneto-aerotaxis in marine coccoid bacteria. Biophys. J. 1997;73:994–1000.
- Blakemore RP. Magnetotactic bacteria. Science. 1975;190:377–379.
- Bazilinski DA, et al. Magnetococcus marinus gen. nov., sp. nov., a marine, magnetotactic bacterium that represents a novel lineage (Magnetococcaceae fam. nov., Magnetococcales ord. nov.) at the base of the Alphaproteobacteria. Int J Syst Evol Microbiol. 2013;63:801–808.
- Bazylinski DA, Frankel RB, Jannasch HW. Anaerobic magnetite production by a marine, magnetotactic bacterium. Nature. 1988;334:518–519.
- Lefèvre CT, et al. Diversity of magneto-aerotactic behaviors and oxygen sensing mechanisms in cultured magnetotactic bacteria. Biophys. J. 2014;107:527–538.
- Brown JM, Wilson WR. Exploiting tumour hypoxia in cancer treatment. Nature Reviews. 2004;4:437–446.
- Wilson WR, Hay MP. Targeting hypoxia in cancer therapy. Nat Rev Cancer. 2011;11(6):393–410.
- Hong M, Zhu S, Jiang Y, Tang G, Pei Y. Efficient tumor targeting of hydroxycamptothecin loaded PEGylated liposomes modified with transferrin. J. Control. Release. 2009;133:96–102.
- Tannock IF, Lee CM, Tunggal JK, Cowan DSM, Egorin MJ. Limited penetration of anticancer drugs through tumor tissue. Clin. Cancer Res. 2002;8:878–884.
- Patyar S, et al. Bacteria in cancer therapy: a novel experimental strategy. J. Biomed. Science. 2010;17:21.
- Schüler D. Formation of magnetosomes in magnetotactic bacteria. J. Molec. Microbiol Biotechnol. 1999;1:79–86.
- de Lanauze D, Felfoul O, Turcot J-P, Mohammadi M, Martel S. Three-dimensional remote aggregation and steering of magnetotactic bacteria microrobots for drug delivery applications. Int. J. Robot. Res. 2014;33(3):359–374.
- McDonald DM, Baluk P. Significance of blood vessel leakiness in cancer. Cancer Res. 2002;62:5381–5385.
- Heldin C-H, Rubin K, Pietras K, Ostman A. High interstitial fluid pressure-an obstacle in cancer therapy. Nat. Rev. Cancer. 2004;4:806–813.
- 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 Nano. 2014;8:5049–5060.
- Préat V. To exploit the tumor microenvironment: Passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. J. Controlled Release. 2010;148:135–146.
- Harrison LB, Chadha M, Hill RJ, Hu K, Shasha D. Impact of tumor hypoxia and anemia on radiation therapy outcomes. Oncologist. 2002;7:492–508.
- Moeller BJ, Richardson RA, Dewhirst MW. Hypoxia and radiotherapy: Opportunities for improved outcomes in cancer treatment. Cancer Metastasis Rev. 2007;26:241–248.
- Polyak B, Friedman G. Magnetic targeting for site-specific drug delivery: applications and clinical potential. Expert Opinion on Drug Delivery. 2009;6:53–70.
- Rotariu O, Strachan NJC. Modelling magnetic carrier particle targeting in the tumor microvasculature for cancer treatment. J. Magnetism and Magnetic Materials. 2005;293:639–646.
- Martel S, et al. Automatic navigation of an untethered device in the artery of a living animal using a conventional clinical magnetic resonance imaging system. Appl. Phys. Lett. 2007;90:114105.
- Dreyfus R, et al. Microscopic artificial swimmers. Nature. 2005;437:862–865.
- Akin D, et al. Bacteria-mediated delivery of nanoparticles and cargo into cells. Nature Nanotechn. 2007;2:441–449.
- Jain RK, Forbes NS. Can engineered bacteria help control cancer? Proc. Natl. Acad. Sci. 2001;98:14748–14750.
- Schübbe S, et al. Complete genome sequence of the chemolithoautotrophic marine magnetotactic coccus strain MC-1. Appl. Environ. Microbiol. 2009;75:4835–4852.
Source: PubMed