Diagnosing lung cancer in exhaled breath using gold nanoparticles

Conventional diagnostic methods for lung cancer1,2 are unsuitable
for widespread screening2,3 because they are expensive and
occasionally miss tumours. Gas chromatography/mass spectrometry
studies have shown that several volatile organic compounds,
which normally appear at levels of 1–20 ppb in healthy
human breath, are elevated to levels between 10 and 100 ppb in
lung cancer patients4–6. Here we show that an array of sensors
based on gold nanoparticles can rapidly distinguish the breath
of lung cancer patients from the breath of healthy individuals in
an atmosphere of high humidity. In combination with solidphase
microextraction7, gas chromatography/mass spectrometry
was used to identify 42 volatile organic compounds
that represent lung cancer biomarkers. Four of these were
used to train and optimize the sensors, demonstrating good
agreement between patient and simulated breath samples.
Our results show that sensors based on gold nanoparticles
could form the basis of an inexpensive and non-invasive diagnostic
tool for lung cancer.

A DNA nanomachine that maps spatial and temporal pH changes inside living cells

Mingxu presented this paper on 4/30/09

Nature Nanotechnology 2009

DNA nanomachines are synthetic assemblies that switch between defined molecular conformations upon stimulation by
external triggers. Previously, the performance of DNA devices has been limited to in vitro applications. Here we report the
construction of a DNA nanomachine called the I-switch, which is triggered by protons and functions as a pH sensor based
on fluorescence resonance energy transfer (FRET) inside living cells. It is an efficient reporter of pH from pH 5.5 to 6.8,
with a high dynamic range between pH 5.8 and 7. To demonstrate its ability to function inside living cells we use the
I-switch to map spatial and temporal pH changes associated with endosome maturation. The performance of our DNA
nanodevices inside living systems illustrates the potential of DNA scaffolds responsive to more complex triggers in
sensing, diagnostics and targeted therapies in living systems.

Carbon nanotubes as photoacoustic molecular imaging agents in living mice

Nature Nanotechnology, 3, 2008, 557

Photoacoustic imaging of living subjects offers higher spatial resolution and allows deeper tissues to be imaged compared with most optical imaging techniques1, 2, 3, 4, 5, 6, 7. As many diseases do not exhibit a natural photoacoustic contrast, especially in their early stages, it is necessary to administer a photoacoustic contrast agent. A number of contrast agents for photoacoustic imaging have been suggested previously8, 9, 10, 11, 12, 13, 14, 15, but most were not shown to target a diseased site in living subjects. Here we show that single-walled carbon nanotubes conjugated with cyclic Arg-Gly-Asp (RGD) peptides can be used as a contrast agent for photoacoustic imaging of tumours. Intravenous administration of these targeted nanotubes to mice bearing tumours showed eight times greater photoacoustic signal in the tumour than mice injected with non-targeted nanotubes. These results were verified ex vivo using Raman microscopy. Photoacoustic imaging of targeted single-walled carbon nanotubes may contribute to non-invasive cancer imaging and monitoring of nanotherapeutics in living subjects16.

Coupling ion channels to receptors for biomolecule sensing

Nature Nanotechnology, 3, 2008, 620

Nanoscale electrical biosensors are promising tools for diagnostics and high-throughput screening systems. The electrical signal allows label-free assays with a high signal-to-noise ratio and fast real-time measurements. The challenge in developing such biosensors lies in functionally connecting a molecule detector to an electrical switch. Advances in this field have relied on synthetic ion-conducting pores1 and modified ion channels2, 3, 4 that are not yet suitable for biomolecule screening. Here we report the design and characterization of a novel bioelectric-sensing platform engineered by coupling an ion channel, which serves as the electrical probe, to G-protein-coupled receptors (GPCRs), a family of receptors that detect molecules outside the cell. These ion-channel-coupled receptors may potentially detect a wide range of ligands recognized by natural or altered GPCRs5, 6, which are known to be major pharmaceutical targets7. This could form a unique platform for label-free drug screening8.

Carbon nanotubes as templates for polymerized lipid assemblies

Nature Nanotechnology, 3, 2008, 743

Amphiphilic molecules—molecules that have both hydrophobic and hydrophilic properties—can self-assemble in water to form diverse structures such as micelles, vesicles and tubes1, 2, 3, and these nanostructures can be used for delivering drugs4, 5, stabilizing membrane proteins6 or as nanoreactors7. We have previously shown that lipids can self-organize on the surface of single-walled carbon nanotubes into regular ring-shaped assemblies8. Here we show that these lipid assemblies can be polymerized and isolated from the nanotube template by application of an electric field. We also demonstrate that these assemblies are monodispersed, water-soluble, and can dissolve various hydrophobic rylene dyes, fullerenes and membrane proteins. The stability of these constructs and their diverse applications will be useful in the fields of cosmetics, medicine and material sciences.

A thixotropic nanocomposite gel for three-dimensional cell culture

Y. Shona Pek, Andrew C. A. Wan, Asha Shekaran, Lang Zhuo & Jackie Y. Ying

Thixotropic materials, which become less viscous under stress and return to their original state when stress is removed, have been used to deliver gel–cell constructs and therapeutic agents. Here we show that a polymer–silica nanocomposite thixotropic gel can be used as a three-dimensional cell culture material. The gel liquefies when vortexed—allowing cells and biological components to be added—and resolidifies to trap the components when the shear force from spinning is removed. Good permeability of nutrients and gases through the gel allows various cell types to proliferate and be viable for up to three weeks. Human mesenchymal stem cells cultured in stiffer gels developed bone-like behaviour, showing that the rheological properties of the gel can control cell differentiation. No enzymatic, chemical, or photo-crosslinking, changes in ionic strength or temperature are required to form or liquefy the gel, offering a way to sub-culture cells without using trypsin—a protease commonly used in traditional cell culture techniques.

http://www.nature.com/nnano/journal/vaop/ncurrent/abs/nnano.2008.270.html

Quantum-dot-assisted characterization of microtubule rotations during cargo transport

Bert Nitzsche, Felix Ruhnow & Stefan Diez

Owing to their wide spectrum of in vivo functions, motor proteins, such as kinesin-1, show great potential for application as nanomachines in engineered environments. When attached to a substrate surface, these motors are envisioned to shuttle cargo that is bound to reconstituted microtubules—one component of the cell cytoskeleton—from one location to another. One potentially serious problem for such applications is, however, the rotation of the microtubules around their longitudinal axis. Here we explore this issue by labelling the gliding microtubules with quantum dots to simultaneously follow their sinusoidal side-to-side and up-and-down motion in three dimensions with nanometre accuracy. Microtubule rotation, which originates from the kinesin moving along the individual protofilaments of the microtubule, was not impeded by the quantum dots. However, pick-up of large cargo inhibited the rotation but did not affect the velocity of microtubule gliding. Our data show that kinesin-driven microtubules make flexible, responsive and effective molecular shuttles for nanotransport applications.

http://www.nature.com/nnano/journal/v3/n9/abs/nnano.2008.216.html

Control of enhanced Raman scattering using a DNA-based assembly process of dye-coded nanoparticles

Duncan Graham, David G. Thompson, W. Ewen Smith & Karen Faulds

Enhanced Raman scattering from metal surfaces has been investigated for over 30 years. Silver surfaces are known to produce a large effect, and this can be maximized by producing a roughened surface, which can be achieved by the aggregation of silver nanoparticles. However, an approach to control this aggregation, in particular through the interaction of biological molecules such as DNA, has not been reported. Here we show the selective turning on of the surface enhanced resonance Raman scattering effect on dye-coded, DNA-functionalized, silver nanoparticles through a target-dependent, sequence-specific DNA hybridization assembly that exploits the electromagnetic enhancement mechanism for the scattering. Dye-coded nanoparticles that do not undergo hybridization experience no enhancement and hence do not give surface enhanced resonance Raman scattering. This is due to the massive difference in enhancement from nanoparticle assemblies compared with individual nanoparticles. The electromagnetic enhancement is the dominant effect and, coupled with an understanding of the surface chemistry, allows surface enhanced resonance Raman scattering nanosensors to be designed based on a natural biological recognition process.

http://www.nature.com/nnano/journal/v3/n9/abs/nnano.2008.189.html

Carbon nanotubes as photoacoustic molecular imaging agents in living mice

Photoacoustic imaging of living subjects offers higher spatial resolution and allows deeper tissues to be imaged compared with most optical imaging techniques. As many diseases do not exhibit a natural photoacoustic contrast, especially in their early stages, it is necessary to administer a photoacoustic contrast agent. A number of contrast agents for photoacoustic imaging have been suggested previously, but most were not shown to target a diseased site in living subjects. Here we show that single-walled carbon nanotubes conjugated with cyclic Arg-Gly-Asp (RGD) peptides can be used as a contrast agent for photoacoustic imaging of tumours. Intravenous administration of these targeted nanotubes to mice bearing tumours showed eight times greater photoacoustic signal in the tumour than mice injected with non-targeted nanotubes. These results were verified ex vivo using Raman microscopy. Photoacoustic imaging of targeted single-walled carbon nanotubes may contribute to non-invasive cancer imaging and monitoring of nanotherapeutics in living subjects.

http://www.nature.com/nnano/journal/v3/n9/abs/nnano.2008.231.html

Remote control of cellular behaviour with magnetic nanoparticles

By binding magnetic nanoparticles to the surface of cells, it is possible to manipulate and control cell function with an external magnetic field. The technique of activating cells with magnetic nanoparticles offers a means to isolate and explore cellular mechanics and ion channel activation to gain better understanding of these processes. Here, we go beyond using this technique as an investigative tool and focus on its potential to actively control cellular functions and processes with an eye towards biological and clinical applications. In particular, we focus on applications in tissue engineering and regenerative medicine.

http://www.nature.com/nnano/journal/v3/n3/abs/nnano.2008.39.html