Nanoneedle Technology Has Drug Delivery, Probe, and Biosensor Applications

Researchers have developed a membrane-penetrating nanoneedle for the targeted delivery of one or more molecules into the cytoplasm or the nucleus of living cells. In addition to transporting miniscule amounts of cargo, the nanoneedle can also be used as an electrochemical probe and as an optical biosensor.

"Nanoneedle-based delivery is a powerful new tool for studying biological processes and biophysical properties at the molecular level inside living cells,” said Min-Feng Yu, a professor of mechanical science and engineering University of Illinois at Urbana-Champaign (USA), and corresponding author of an article accepted for publication in Nano Letters, and posted on the journal's web site in May 2009.

In the study, Prof. Yu and collaborators described how they deliver, detect, and track individual fluorescent quantum dots in a cell's cytoplasm and nucleus. The quantum dots can be used for studying molecular mechanics and physical characteristics inside cells.

To create a nanoneedle, the researchers begin with a rigid but resilient boron-nitride nanotube. The nanotube is then attached to one end of a glass pipette for easy handling, and coated with a thin layer of gold. Molecular cargo is then attached to the gold surface via "linker” molecules. When placed in a cell's cytoplasm or nucleus, the bonds with the linker molecules break, freeing the cargo.

With a diameter of approximately 50 nm, the nanoneedle introduces minimal intrusiveness in penetrating cell membranes and accessing the interiors of live cells. The delivery process can be precisely controlled, monitored, and recorded--goals that have not been achieved in prior studies. "The nanoneedle provides a mechanism by which we can quantitatively examine biological processes occurring within a cell's nucleus or cytoplasm,” said Yang Xiang, a professor of molecular and integrative physiology and a coauthor of the article. "By studying how individual proteins and molecules of DNA or RNA mobilize, we can better understand how the system functions as a whole.”

The ability to deliver a small number of molecules or nanoparticles into living cells with spatial and temporal precision may make feasible numerous new strategies for biologic studies at the single-molecule level, which would otherwise be technically challenging or even impossible, the researchers reported. "Combined with molecular targeting strategies using quantum dots and magnetic nanoparticles as molecular probes, the nanoneedle delivery method can potentially enable the simultaneous observation and manipulation of individual molecules,” said Ning Wang, a professor of mechanical science and engineering and a coauthor of the study.

Beyond the delivery process, the nanoneedle-based approach can also be extended in many ways for single-cell studies, according to Prof. Yu, who also is a researcher at the Center for Nanoscale Chemical-Electrical-Mechanical Manufacturing Systems. "Nanoneedles can be used as electrochemical probes and as optical biosensors to study cellular environments, stimulate certain types of biological sequences, and examine the effect of nanoparticles on cellular physiology.”

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