Using a complex imaging system, researchers could show the journey of varying types of nanoparticles as they enter the body from the pulmonary system
Scientists from the Beth Israel Deaconess Medical Center (BIDMC; MA, USA) and the Harvard School of Public Health, MA, USA, have investigated the journey of nanoparticles from the lungs into the body in an exciting new study. The near-infrared fluorescent nanoparticles were tracked as they moved from the airspace of the lungs into the body and out again, using a novel, real-time imaging system.
The knowledge of the characteristics and behavior of nanoparticles in the pulmonary system has great potential in developing therapeutic agents to treat pulmonary disease, as well as providing a better understanding of the health effects of air pollution. The specific anatomy of the lung, including a large surface area and minimal barriers limiting access to the body, make it a particularly good target for nanoparticle drug delivery. “We have been interested in the fate of small particles after they deposit deep in the gas exchange region of the lung,” explained Akira Tsuda, a research scientist at the Harvard School of Public Health. “Determining the physicochemical characteristics of inhaled nanoparticles on their ability to cross the (lungs) alveolar epithelial surface is an important step in understanding the biological effects associated with exposure to these particles.”
This new research was made possible with the use of the fluorescence-assisted resection and exploration (FLARE™) imaging system. The imaging system was used to track the movement of a group of near-infrared fluorescent nanoparticles, varying in chemical composition, size, shape and surface charge, within the lungs of rat models over a period of 1 h. The conditions were varied in order for the physiochemical properties of the various engineered particles to be clarified. “The FLARE system enabled us to cut the number of experiments in half while performing direct comparisons of nanoparticles of different sizes, shapes and rigidities,” explained co-senior author John V Frangioni, of the Division of Hematology/Oncology at BIDMC, whose laboratory developed the FLARE system for use in image-guided cancer surgery as well as other applications.
The results, verified using conventional radioactive tracers, established that nonpositively charged nanoparticles, smaller than 34 nm in diameter, appeared in the lung-draining lymph nodes within 30 min, while those smaller than 6 nm in diameter, with ‘zwitterionic’ (i.e., equal positive and negative charge) characteristics, traveled to the draining lymph nodes within just a few minutes. “These new findings can be applied to design and optimize particles for drug delivery by inhalation therapy,” noted Tsuda. “This research also guides us in the assessment of the health effects of various particulate pollutants, as the data suggest the importance of distinguishing specific subclasses of particles (based on surface chemistry and size) that can rapidly cross the alveolar epithelium and may disseminate in the body.” As Frangioni concluded, “We‘ve now described a complete ‘cycle’ of nanoparticle trafficking – from the environment, through the lungs, into the body, then out of the kidneys in urine and back to the environment.”
Sources: Beth Israel Deaconess Medical Center, Boston, MA, USA: www.bidmc.org/News/InResearch/2010/November/Nanoparticles.aspx; Choi HS, Ashitate Y, Lee JH et al.: Rapid translocation of nanoparticles from the lung airspaces to the body. Nat. Biotechnol. (2010) (Epub ahead of print).
Scientists could map out the eye‘s neural network using a sophisticated 519-electrode array
Researchers from the School of Physics and Astronomy at the University of Glasgow, UK, working in collaboration with Stanford University, CA, USA, and the University of California Santa Cruz, CA, USA, have mapped the neural circuitry involved in processing color vision in humans for the first time. The pattern of connectivity between cone receptor cells and ganglion cells, two types of cell involved with the interpretation of color, has been revealed by the researchers following analysis using a unique 519-electrode array. As Deborah Gunning, who worked on developing the technology during her PhD studies at the University of Glasgow, enthused, “This is an exciting example of interdisciplinary science with experts in neuroscience, nanoengineering, physics and electronics combining to perform cutting-edge science.”
This breakthrough reveals how the different cone receptor cells within the retina communicate with the output cells to build up a color picture. The retina consists of a layered structure of neural tissue with input cells (photoreceptors), processing cells and output cells (ganglion cells). While it is understood that color perception arises from the comparison of signals received by different cone cells, one of the two types of photoreceptor cells, exactly how these signals were combined by the retina and transmitted by the ganglion cells to the brain has remained unproven. Using the 519-electrode array, the researchers have been able to record neural signals at high speed and with fine spatial detail, thus sufficiently detecting a population of tiny, densely spaced output cells known as ‘midget’ retinal ganglion cells. “The electrode array we developed enabled us to measure the retinal output signals of hundreds of cells simultaneously and create a map of the input–output relationship at an unprecedented resolution and scale,” explained Keith Mathieson, a research fellow within the School of Physics and Astronomy at the University of Glasgow but currently based at Stanford University and the University of California Santa Cruz, who played a key role in the research.
The research holds great promise for the development of potential future treatments for vision-related diseases and disorders. As Mathieson concluded, “To develop new therapies for vision-related problems it is necessary to fully understand how the retina works. This research gives us a much greater insight into the circuitry of the retina and is an important development for neuroscience.”
Sources: The University of Glasgow, UK: www.gla.ac.uk/news/headline_179047_en.html; Field GD, Gauthier JL, Sher A et al.: Functional connectivity in the retina at the resolution of photoreceptors. Nature 467(7316), 673–677 (2010). Novel nanogenerator developed using nanotechnology combined with piezoelectrics
Materials are able to convert biomechanical forces from the human body into electrical energy
New forms of highly efficient, flexible nanogenerator technology have been developed using freely bendable piezoelectric ceramic thin-film nanomaterials. These materials are able to convert tiny movements of the human body, such as heartbeats and blood flow, into electrical energy, which has great potential for future medical applications.
The research team was led by Keon Jae Lee from the Korea Advanced Institute of Science and Technology (KAIST, South Korea), and Zhong Lin Wang study from the Georgia Institute of Technology, Atlanta, GA, USA. Wang invented the bio-eco-friendly ceramic thin film nanogenerator, which is freely bendable without breakdown. As he described, “This technology can be used to turn on an LED by slightly modifying circuits and operate touchable flexible displays. In addition, thin film nanomaterials (‘barium titanate‘) of this research have the property of both high efficiency and lead-free biocompatibility, which can be used in future medical applications.”
Nanogenerator technology combines nanotechnology with piezoelectrics, where voltage can be generated when pressure or bending strength is applied to piezoelectric materials. This technology has great potential for application in bioimplantable sensors, since biomechanical forces produced by the human body have inherent capabilities for infinite production of nonpolluting energy.
Sources: Georgia Institute of Technology, Atlanta, GA, USA: www.gatech.edu/newsroom/release.html?nid=62640; Park KI, Xu S, Liu Y et al.: Piezoelectric BaTiO(3) Thin film nanogenerator on plastic substrates. Nano Lett. (2010) (Epub ahead of print).
New drug-engineering technology has been used in an approach to target a protein directly involved with brain tumor growth, which was identified in 2001. This is believed to be the first known application of a pH-dependent endosome-escape unit in drugs administered intravenously for brain cancer treatment. “This nanobioconjugate is different from earlier nanomedicine drugs because it delivers and releases antitumor drugs within tumor cells, not just at the site of a tumor,” research scientist and senior author of the paper, Julia Y Ljubimova, explained.
The research, reported by scientists at the Maxine Dunitz Neurosurgical Institute at the Cedars-Sinai Medical Center, CA, USA, was initiated nearly a decade ago, when a subtle shift was detected in the molecular make-up of glioblastoma multiforme, the most aggressive type of brain tumor. Laminin-411 was the protein discovered to play a major role in the tumor‘s ability to build new blood vessels, essential in supporting its growth and spreading. However, it is only now that suitable nanomedicine technology exists in order to be able to block this protein. The research team has created a ‘nanobioconjugate’ drug, which would be given by intravenous injection and carried in the blood to target the brain tumor. The drug has been engineered to specifically permeate the tumor cell wall and enter endosomes, which in turn trigger a chemical component of the drug as they mature and their internal pH lowers. The trigger causes the endosomes’ membranes to break and the released drugs then block the tumor cell‘s production of laminin-411.
The drug is a macromolecule of 20–30 nm in size and is based on a highly purified form of polymalic acid, derived from the single cell organism Physarum polycephalum. It is nontoxic to nontumor cells, thus side effects associated with conventional chemotherapy are not an issue. The nanoconjugate is also digested completely by the body once it has performed its task within the tumor cell, thus there is no harmful residue. As Ljubimova enthuses, “Based on our studies, this nanoconjugate appears to be a safe and efficient delivery platform that may also be appropriate in the treatment of degenerative brain conditions and a wide array of other disorders. It is harmlessly degraded to carbon dioxide and water, nontoxic to normal tissue, and, unlike some drugs, it is nonimmunogenic, meaning that it does not stimulate the immune system to the point of causing allergic reactions that can range from mild coughs or rashes to sudden, life-threatening symptoms.”
Sources: Cedars-Sinai Medical Center, CA, USA: www.cedars-sinai.edu/About-Us/News/News-Releases-2010/Cedars-Sinai-Nano-Drug-Hits-Brain-Tumor-Target-Found-in-2001.aspx; Ding H, Inoue S, Ljubimov AV et al.: Inhibition of brain tumor growth by intravenous poly(b-L-malic acid) nanobioconjugate with pH-dependent drug release. Proc. Natl Acad. Sci. USA 107(42), 18143–18148 (2010).