Gadolinium-based nanoparticles exhibit efficient upconversion of light that could be used for bioimaging in the body.
A team of researchers from the National University of Singapore (Queenstown, Singapore), King Abdullah University of Science and Technology (Thuwal, Saudi Arabia) and the Chinese Academy of Sciences (Fujian, China) have developed an efficient upconversion process using gadolinium-based nanoparticles, which could have a potential application in bioimaging and biolabeling of cancer cells.
In the study, Associate Professor Xiaogang Liu and his team used nanoparticles with core–shell structures that allowed fine-tuning of upconversion emission through energy migration. The ability of these nanoparticles to convert low-energy near-infrared light into high-energy visible emission means they may have a wide range of applications. In one set of experiments gadolinium-based nanoparticles were doped with different lanthanide ions. Energy transfer between the particles was evident and measured by emission spectroscopy. The nanoparticles demonstrated multiple upconversion emission colours with infrared excitation wavelengths longer than 980 nm. The transparency of living tissues is high in infrared light, thus excitation of the nanoparticles with this wavelength of light enhances their use in cancer cell detection. Liu explained that coupling the nanoparticles to biological molecules could lead to a rapid and reliable way of detecting cancer and other diseases. Commenting on the results of his team Liu said that the importance of the work was twofold. “Firstly we demonstrated that the core-shell structural engineering enables fine-tuning of upconversion emission through energy migration. This presents a significant technological advance in the rational design and preparation of luminescent materials. The second major advance of our work is the design and discovery of interparticle energy migration through lanthanide-doped nanoparticle acceptors. We believe this offers a unique solution to a long-standing problem in the field of energy transfer involving lanthanide-doped nanophosphors as the energy acceptors.”
The use of upconversion materials in imaging applications removes the difficulty of distinguishing the optical signal from the background emission. Liu explained the choice for the core-shell structure and the reasoning behind the gadolinium-based nanoparticles. “Efficient photo upconversion is generally restricted to only three lanthanide ions (Er3+, Tm3+ and Ho3+). These three lanthanides emit visible light that only covers a small portion of the visible spectral region. This limits applications such as color tuning or multiplex biolabeling. We use a gadolinium dopant for energy migrating that enables upconverted emission from other lanthanides (Tb3+, Eu3+, Dy3+ and Sm3+). The use of a core-shell design avoids excitation energy quenching or cross-relaxation between lanthanide ions.” The nontoxicity nonblinking characteristics of these nanoparticles adds to their potential for use in vivo.
Commenting on the next steps for his team‘s work Liu said, “The next step would be the application of these nanoparticles for biolabeling and bioimaging. We also plan to design experiments that enable a better understanding of the upconversion mechanism in these nanoparticles. One big challenge is to dope transition metal ions along with the lanthanides for broader applications.”
– By Hannah Stanwix
Sources: Wang F, Deng R, Wang J et al. Tuning upconversion through energy migration in core–shell nanoparticles. Nat. Mater. 10(12), 968–973 (2011); National University of Singapore Press Release 14 November 2011, “Novel nanocrystals with advanced optical properties developed for use as luminescent biomarkers”: www.physorg.com/news/2011-11-nanocrystals-advanced-optical-properties-luminescent.html
An immunosensor using carbon nanotubes demonstrates specific Salmonella detection.
Researchers from the University of Pennsylvania (PA, USA) and Alabama State University (AL, USA) have developed a biosensor using carbon nanotube devices that can specifically detect Salmonella in nutrient broth complexes.
The nanotube transistors were functionalized with covalently bound anti-Salmonella antibodies. The devices were exposed to Salmonella at various different concentrations in an incubator at 37°C for 45 min. The researchers found that the ON-state current of the nanotube transistors sharply decreased, by approximately 80%, on exposure to Salmonella. Professor Johnson, one of the lead authors of the study, explained the relevance of the findings. “We focused on detection in a complex nutrient broth that resembles real foodstuffs at harvest or point of use. We found sensitivity comparable to that of earlier work on Salmonella in low-salt buffer, demonstrating the promise of nanotube-based biosensors for this application.” According to Johnson, pathogen detection in this kind of ‘real-world’ setup was a key issue that had not been previously addressed in earlier studies.
The use of carbon nanotubes in sensors is not novel, and Johnson described why their properties make them ideal. “Carbon nanotubes are excellent candidates for signal transduction elements because of their high sensitivity and compatibility with conventional readout electronics. Moreover, their surface chemistry is well understood, so it is straightforward to create chemical linkages to antibodies.”
The study could represent a step forward in using carbon nanotubes sensors to detect bacteria. Commenting on the next steps for his research Johnson said there were several interesting aspects still to be explored, such as the use of engineered antibodies or antibody fragments to enhance sensitivity even further, and the implementation of large arrays of nanotube sensors for detection of multiple pathogens simultaneously.
– By Hannah Stanwix
Source: Lerrner MB, Goldsmith BR, McMillon R et al. A carbon nanotube immunosensor for Salmonella. AIP Advances 1, 042127 (2011).
A polymer nanocomposite probe based on the skin of the sea cucumber could be used to treat neurological disorders.
A group of researchers from Case Western Reserve University (Cleveland, OH, USA), Harvard Medical School (Boston, MA, USA), Massachusetts General Hospital (Boston, MA, USA) and the University of Fribourg (Fribourg, Switzerland) have developed a hard polymer nanocomposite probe that becomes softer and more pliable upon insertion in to the cerebral cortex. The probe could be used for studying and treating neurological disorders.
The team found that, after implanting the device in to the cerebral cortex of rats, the brain‘s immune response was different to that when a conventional metal probe was implanted; it appeared that the brain was able to heal faster. Some 15 min after implantation the initial tensile storage modulus of the nanocomposite probe reduced from 5 GPa to 12 MPa. A total of 4 weeks after implantation the neuronal nuclei density within 100 µm of the probe was greater for the nanocomposite compared with a stiff wire probe. After 8 weeks following implantation the neuronal nuclei density around the wire probe had increased to match that of the nanocomposite. However, encouragingly, the researchers noted that the glial scar response to the nanocomposite probe was less than that to the stiff wire.
The probe‘s design was based on the skin of the sea cucumber, which is normally soft and flexible, but becomes hard upon touching, an intriguing defence mechanism. The nanocomposite is formed from short poly(vinylacetate) chains linked together to form a rigid network, necessary to allow insertion of the probe in to the cerebral cortex. When this network comes in to contact with water the linkages begin to degrade, meaning the nanocomposite rapidly becomes softer. It is thought that the mechanical mismatch between brain tissue and the probe cause an inflammatory response, so by designing a mechanically adaptive probe the researchers hope to avoid this problem.
Concluding their study the team indicated the possible future paths for this research, which include further developing these mechanically adaptive materials and investigating the neuroprotective pathways in the brain.
– By Hannah Stanwix
Source: Harris JP, Capadona JR, Miller RH et al. Mechanically adaptive intracortical implants improve the proximity of neuronal cell bodies. J. Neural Eng. 8(6), 066011 (2011).
A molecularly targeted nanoformulation of docetaxel has proven effective as a radiosensitizer for tumor cells, according to a recent study.
Using biodegradable and biocompatible lipid–polymer nanoparticles and folate as a molecular-targeting ligand, a team of researchers led by Andrew Wang (University of North Carolina, Chapel Hill, NC, USA) have engineered a folate-targeted nanoparticle formulation of docetaxel, which has been shown in a recent study to improve the efficiency of chemoradiotherapy.
The team synthesized nanoparticles of 72 ± 4 nm in size, and conducted in vitro and in vivo radiosensitization studies. In vitro, the group found that the nanoformulation of docetaxel was as effective as conventional docetaxel as a radiosensitizer when irradiation was administered at the optimal time of 24 h. However, in vivo studies showed that the folate-targeted nanoformulation was significantly more effective than either docetaxel alone or a nontargeted nanoparticle formulation of docetaxel. Wang commented on the findings reported in the study. “Our results showed that nanoparticle docetaxel is more effective than docetaxel in chemoradiotherapy and the efficacy may depend on the timing of radiotherapy. Both of the findings hold major clinical implications. First, our results support that nanoparticle therapeutics can improve chemoradiotherapy, which can lead to improved cancer cure and improved quality of life for patients. Second, we have identified a key factor for the clinical utilization of polymeric nanoparticle docetaxel.” Expanding further on the finding that the timing of irradiation is critical to the effectiveness of the treatment, Wang noted, “The timing dependence is a novel phenomenon and suggests that polymeric nanoparticle docetaxel may function differently than docetaxel. We are currently trying to identify the exact mechanism for this finding.”
Currently, chemoradiotherapy is an effective treatment for many solid tumor cancers; however, researchers are striving to improve the therapeutic index of this treatment method. Wang explained why nanoparticles could be ideal. “We believe the use of nanoparticle therapeutics provides an exciting and unprecedented opportunity to accomplish this goal. Nanoparticles have very unique biodistributions concentrated in tumors and the liver but minimal in other normal organs, such as the lungs. The difference in drug concentration between the tumor and the surrounding tissue is much greater than that of small molecule drugs. Since radiotherapy is aimed at the tumor and surrounding tissue, nanoparticle therapeutics can lead to higher efficacy but lower toxicity.”
Wang and his coworkers plan to move this research towards clinical trials, as well as developing other nanoformulations of chemotherapeutics. “We are developing nanoparticle formulations of existing chemotherapeutics and comparing them to their small molecule counterparts. We are also evaluating two commercial nanoparticle docetaxel formulations in the laboratory in preparation for clinical trials in the coming year.” This study shows the potential promise for molecularly targeted nanoparticles in chemoradiotherapy.
– By Hannah Stanwix
Source: Werner ME, Copp JA, Shrirang K et al. Folate-targeted polymeric nanoparticle formulation of docetaxel is an effective molecularly targeted radiosensitizer with efficacy dependent on the timing of radiotherapy. ACS Nano 5(11), 8990–8998 (2011).