We are extremely excited and thankful to the American Cancer Society and the Harper Cancer Research Institute for facilitating this seed grant for our work on label-free targeting of undruggable cancer cells.
We intend to target non-targetable cancer cells by tuning the force exerted by label-free nanomaterials at the cell membrane to selectively permeabilize the more compliant cancer cell membranes but not the stiffer healthy cell membranes.
Systemic delivery of chemotherapeutics is toxic to all cells but more so to cancer cells due to the high metabolic rate of cancer cells. Targeted drug delivery using antibody tagged drug carriers reduce the dosage required to kill cancer cells and thereby mitigate the toxicity associated with systemic drug delivery. But the lack of unique targetable biomarkers on aggressive cancer cells such as 3º negative breast cancer makes targeted drug delivery option a non-starter. But with the recent advances in biophysics, it is well documented that cancer cells have significantly different cell membrane stiffness in comparison to healthy cells. Cancer cell membranes are less stiff, more compliant and the cells as a whole are easily deformable. The difference in membrane physical properties can be exploited by applying a force that is above the threshold required to permeabilize the cancer cells, but the force is still below the threshold required to permeabilized normal cells.
We have been funded to demonstrate a proof-of-concept delivery of doxorubicin to triple-negative breast cancer cells in a syngeneic mouse model.
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