May 22, 2009 Nanomaterials less than 100-thousand-millionths of a meter in size have the potential to radically change current drug delivery techniques with early trials showing the ability of nanomaterials to moderate the release of highly toxic chemotherapy drugs and other therapeutics with both reduced side effects and improved targeting. Using nanodiamonds, researchers at the McCormick School of Engineering and Applied Science have demonstrated a new tool designed to precisely deliver tiny doses of drug-carrying to individual cells - the Nanofountain Probe.
The team led by Prof. Horacio Espinosa and Assist. Prof. Dean Ho have shown that these nanomaterials can shuttle chemotherapy drugs to cells without producing the negative effects of today's delivery agents. Clusters of the nanodiamonds surround the drugs to ensure that they remain separated from healthy cells until they reach the cancer cells, where they are released. Further good news is that these nanodiamonds have been shown not to induce inflammation in cells once they've done their job.
The Nanofountain Probe, functions in two different ways: in one mode, the probe acts like a fountain pen, wherein drug-coated nanodiamonds serve as the ink, allowing researchers to create devices by "writing" with it. The second mode functions as a single-cell syringe, permitting direct injection of biomolecules or chemicals into individual cells.
The group used the Nanofountain Probe to injected tiny doses of nanodiamonds into both healthy and cancerous cells, a technique that Espinosa and Ho believe will help cancer researchers investigate the effectiveness of new drug-nanomaterial systems as they become available. The group also used the probe to pattern dot arrays of drug-coated nanodiamonds directly on glass substrates. These dots can be made smaller than 100 nanometers in diameter and Espinosa says that this provides the proof of concept by which to manufacture devices that will deliver these nanomaterials within the body.
The work addresses two major challenges in the development and clinical application of nanomaterial-mediated drug-delivery schemes: dosage control and high spatial resolution. “This is an exciting development that complements our previous demonstrations of direct patterning of DNA, proteins and nanoparticles,” says Espinosa.
A key restraint in fundamental R&D is the ability to deliver drugs into a single cell and as such the scientists are restricted to the impact of the drug on a whole cell population. The team has overcome this constraint in being able to inject single cells using the probe.
“This allows us to deliver a precise dose to one cell and observe its response relative to its neighbors,” Ho says. “This will allow us to investigate the ultimate effectiveness of novel treatment strategies via a spectrum of internalization mechanisms.”
In previous work Ho and his colleagues developed a patch to deliver chemotherapy drugs locally to sites where cancerous tumors have been removed. The patch is embedded with a layer of drug-coated nanodiamonds, which moderate the release of the drug over a period of months, reducing the need for chemotherapy following the removal of a tumor. “An attractive enhancement will be to use the Nanofountain Probe to replace the continuous drug-nanodiamond films currently used in these devices with patterned arrays composed of multiple drugs,” Ho says. “This allows high-fidelity spatial tuning of dosing in intelligent devices for comprehensive treatment.”
Another aspect of the work being conducted by the group is the delivery of a wide variety of bio-agents, including DNA, viruses and other therapeutically relevant materials. Another key application is based on the the ability of the probe to pattern nanodiamonds with sub-100 nanometer layers. This represents an improvement of three orders of magnitude on other reported direct-write schemes and provides inroads to realizing these devices on a mass scale.
The work was supported by the National Science Foundation, the National Institutes of Health, the V Foundation for Cancer Research and the Wallace H. Coulter Foundation and the results were recently published online in the scientific journal Small.
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