Chemotherapy — the therapeutic introduction of chemical toxins to cancerous tissue — can lose its effectiveness relatively quickly. Due primarily to a strongly conserved, pumping mechanism, known as cell efflux, chemo-resistant tumor cells are able to rapidly pump the anti-tumor chemicals out of the cell, rendering the chemotherapy much less effective. Pumped-out chemotoxins end up building up in extracellular tissue and sometimes killing healthy cells. This add both to the pain, and cost, of chemo.
But the key to enhancing the therapy lies in the chemistry and the geometry of simple carbon crystals known as nanodiamonds.
A team of bio-medical engineers led by Dean Ho of Northwestern university (Evanston, Illinois), are using nanodiamonds to cleverly exploit a flaw in the cell’s pumping system and boost the effectiveness of the anti-tumor medicine.
The diamonds are all eight-sided carbon structures (“truncated octahedrals”) measuring just a few billionths of a meter in size (hence nano). Though simpler in form than the one picture above, these nanostructures likewise have facets, with some facets carrying a negative charge and others being electrically neutral. This means that an additional chemical — such as the chemo agent doxorubicin — can be attached to them, and then later, inside the cell, be released and dispersed.
Nanodiamonds have another useful property: their geometry doesn’t fit with the shape of the proteins that make up the tumor cell’s efflux pump. Hence, the diamonds stay inside the cell longer, boosting the effectiveness of the chemotherapy treatment, and inducing greater cell death. What’s more, the use of nanodiamonds as agents for chemo delivery seems to greatly reduce the toxic side effects of the therapy (as determined through a mouse model).
The team administered two different treatments to two groups of mice with liver tumors — the first treatment consisted of the nanodiamond-doxorubicin combo (called NDX), and the second with doxorubicin alone. After two days the liver tumors were biopsied and analyzed. The results: mice treated with the nanodiamond compound had cellular levels of doxorubicin ten times higher than those mice treatment with the chemo drug alone. Further, tumor size was reduced more and life span extended in mice receiving NDX.
An additional experiment was performed using the NDX preparation on mammary carcinoma models with similar positive results.
Quoting from the research paper abstract:
” A complex (NDX) of ND and doxorubicin (Dox) overcame drug efflux and significantly increased apoptosis and tumor growth inhibition beyond conventional Dox treatment in both murine liver tumor and mammary carcinoma models.”
And if that weren’t enough, nanodiamonds are both scalable and bio-compatible. They appear to be non-toxic/non-inflammatory, and, are very cheap to produce in bulk, making this treatment, if validated by others, perhaps the most cost-effective treatment (for both patient and provider) in our cancer-fighting toolkit.
And while researchers acknowledge that the “ND-conjugated chemotherapeutic” technique needs some refining (perhaps through using synthetic polymers in place of the diamonds), these are compelling and highly encouraging results and these experiments further extend the successful application of nanotechnology into the medical sciences.
Let us not forget either the humble laboratory mouse, whose perfected progeny are the bedrock of modern medicine.
Results of the experiments were published in the Journal Science Translational Medicine (March 9, 2011) under the title: Nanodiamond Therapeutic Delivery Agents Mediate Enhanced Chemoresistant Tumor Treatment.
Team members include: Edward K. Chow, Xue-Qing Zhang, Mark Chen, Robert Lam, Erik Robinson, Houjin Huang, Daniel Schaffer, Eiji Osawa, Andrei Goga, and Dean Ho.
Top image: Tetracube ; CC – By 3.0 ; Explanation: An omnitruncated tesseract perspective projection centered on one of the truncated octahedral cells, highlighted in yellow (this is the basic geometric shape of the ND particles). Four of the surrounding hexagonal prisms are shown in blue, with 4 more truncated octahedra on the other side of these prisms also shown in yellow. Cells obscured from 4D viewpoint culled for clarity’s sake.
Lab Mouse Photo: Rama ; CC – BY – SA 2.0