August 15, 2016

Magnetically guided bacteria with drug-containing nanoliposomes delivered what would have been toxic to human anticancer treatment to kill resistant cancer tumors

Researchers from Polytechnique Montréal, Université de Montréal and McGill University have just achieved a spectacular breakthrough in cancer research. They have developed new nanorobotic agents capable of navigating through the bloodstream to administer a drug with precision by specifically targeting the active cancerous cells of tumors. This way of injecting medication ensures the optimal targeting of a tumor and avoids jeopardizing the integrity of organs and surrounding healthy tissues. As a result, the drug dosage that is highly toxic for the human organism could be significantly reduced.

This scientific breakthrough has just been published in the prestigious journal Nature Nanotechnology in an article titled “Magneto-aerotactic bacteria deliver drug-containing nanoliposomes to tumor hypoxic regions.” The article notes the results of the research done on mice, which were successfully administered nanorobotic agents into colorectal tumours.


MC-1 cells are preferentially located in the hypoxic regions of the xenografts

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



“These legions of nanorobotic agents were actually composed of more than 100 million flagellated bacteria – and therefore self-propelled – and loaded with drugs that moved by taking the most direct path between the drug’s injection point and the area of the body to cure,” explains Professor Sylvain Martel, holder of the Canada Research Chair in Medical Nanorobotics and Director of the Polytechnique Montréal Nanorobotics Laboratory, who heads the research team’s work. “The drug’s propelling force was enough to travel efficiently and enter deep inside the tumors.”

When they enter a tumor, the nanorobotic agents can detect in a wholly autonomous fashion the oxygen-depleted tumor areas, known as hypoxic zones, and deliver the drug to them. This hypoxic zone is created by the substantial consumption of oxygen by rapidly proliferative tumour cells. Hypoxic zones are known to be resistant to most therapies, including radiotherapy.

But gaining access to tumors by taking paths as minute as a red blood cell and crossing complex physiological micro-environments does not come without challenges. So Professor Martel and his team used nanotechnology to do it.

Bacteria with compass

To move around, bacteria used by Professor Martel’s team rely on two natural systems. A kind of compass created by the synthesis of a chain of magnetic nanoparticles allows them to move in the direction of a magnetic field, while a sensor measuring oxygen concentration enables them to reach and remain in the tumor’s active regions. By harnessing these two transportation systems and by exposing the bacteria to a computer-controlled magnetic field, researchers showed that these bacteria could perfectly replicate artificial nanorobots of the future designed for this kind of task.

“This innovative use of nanotransporters will have an impact not only on creating more advanced engineering concepts and original intervention methods, but it also throws the door wide open to the synthesis of new vehicles for therapeutic, imaging and diagnostic agents,” Professor Martel adds. “Chemotherapy, which is so toxic for the entire human body, could make use of these natural nanorobots to move drugs directly to the targeted area, eliminating the harmful side effects while also boosting its therapeutic effectiveness.”

“These results represent a novel therapeutic avenue for patients with hard-to-treat cancers, once the approach has been validated in human trials,” says co-author Nicole Beauchemin, a professor of Biochemistry, Medicine and Oncology at McGill and researcher at the Rosalind and Morris Goodman Cancer Research Centre. “The combination of multiple expertise from all team members has made this project possible; it represents for me one of the most exciting scientific projects I have ever tackled.” Other co-authors include researchers from McGill’s departments of Biomedical Engineering and Oncology, the Faculty of Dentistry, the McGill University Health Centre Research Institute, and the Jewish General Hospital.

Abstract - Magneto-aerotactic bacteria deliver drug-containing nanoliposomes to tumor hypoxic regions

Oxygen-depleted hypoxic regions in the tumor 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 behavior of magnetotactic bacteria, Magnetococcus marinus strain MC-1, can be used to transport drug-loaded nanoliposomes into hypoxic regions of the tumor. 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 tumor 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 tumor hypoxic regions.

SOURCES - Polytechnique Montréal, Université de Montréal and McGill University, Nature Nanotechnology

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