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Researchers discover why nanoparticles have yet to deliver clinical benefits.
Posted On: January 06, 2017
Nanoparticles are a promising strategy for treating cancer: they can be chemically linked to drugs that kill cancerous cells; and they can also be linked to imaging agents that help guide tumour removal. While these strategies often work in experimental models (ie, lab petri dishes), they fail when nanoparticles are used in patients because most of the nanoparticles become trapped and accumulate in the liver or spleen.
A new study by TGHRI Scientist Dr. Ian McGilvray and University of Toronto Scientist Dr. Warren Chan has revealed that this may be related to how nanoparticles interact with the cells they encounter.
The researchers report that when nanoparticles enter the liver from the blood stream, they slow down and move a thousand times slower, which enables them to interact with the cells. During this interaction some of the nanoparticles are ingested by liver cells and eliminated from the body. Nanoparticles that escape these interactions return to the blood stream but are ultimately carried back to the liver. This process of removal was similar for all the nanoparticles tested regardless of the type of material used or the nanoparticle design.
“This is the first detailed glimpse into the biological mechanism by which these particles are eliminated from the body,” explains Dr. McGilvray. “It suggests that strategies for improving the effects of nanomedicines should not only consider nanomaterial design but also conditioning of the liver to reduce nanoparticle removal.”
This work was supported by the Canadian Institute of Health Research, the Natural Sciences and Engineering Research Council, the Surgeon-Scientist Program at the University of Toronto and the Toronto General & Western Hospital Foundation.
Tsoi KM, MacParland SA, Ma XZ, Spetzler VN, Echeverri J, Ouyang B, Fadel SM, Sykes EA, Goldaracena N, Kaths JM, Conneely JB, Alman BA, Selzner M, Ostrowski MA, Adeyi OA, Zilman A, McGilvray ID, Chan WC. Mechanism of hard-nanomaterial clearance by the liver. Nat Mater. 2016 Aug 15. doi: 10.1038/nmat4718. [PubMed abstract]
A new study by TGHRI Scientist Dr. Ian McGilvray and University of Toronto Scientist Dr. Warren Chan has revealed that this may be related to how nanoparticles interact with the cells they encounter.
The researchers report that when nanoparticles enter the liver from the blood stream, they slow down and move a thousand times slower, which enables them to interact with the cells. During this interaction some of the nanoparticles are ingested by liver cells and eliminated from the body. Nanoparticles that escape these interactions return to the blood stream but are ultimately carried back to the liver. This process of removal was similar for all the nanoparticles tested regardless of the type of material used or the nanoparticle design.
“This is the first detailed glimpse into the biological mechanism by which these particles are eliminated from the body,” explains Dr. McGilvray. “It suggests that strategies for improving the effects of nanomedicines should not only consider nanomaterial design but also conditioning of the liver to reduce nanoparticle removal.”
This work was supported by the Canadian Institute of Health Research, the Natural Sciences and Engineering Research Council, the Surgeon-Scientist Program at the University of Toronto and the Toronto General & Western Hospital Foundation.
Tsoi KM, MacParland SA, Ma XZ, Spetzler VN, Echeverri J, Ouyang B, Fadel SM, Sykes EA, Goldaracena N, Kaths JM, Conneely JB, Alman BA, Selzner M, Ostrowski MA, Adeyi OA, Zilman A, McGilvray ID, Chan WC. Mechanism of hard-nanomaterial clearance by the liver. Nat Mater. 2016 Aug 15. doi: 10.1038/nmat4718. [PubMed abstract]