The pros and cons of inhaled nanoparticles: IR fluorescence reveals all

Ezine

Published: Dec 1, 2010
Author: David Bradley
Channels: Infrared Spectroscopy

thumbnail image: The pros and cons of inhaled nanoparticles: IR fluorescence reveals all

Imaging nanoparticles in the breath

A new imaging system based on near-infrared fluorescent nanoparticles can provide a real-time understanding of how such tiny particles get into the airspaces within the lungs. The description of the inhalation of such experimental particles could be used to help medical researchers develop therapeutic agents for treating pulmonary disease, as well as offering a greater understanding of the health effects of air pollution.

In work partly supported by grants from the National Institutes of Health, Yoshitomo Ashitate, Jeong Heon Lee, Soon Hee Kim and Aya Matsui of the Beth Israel Deaconess Medical Center (a Harvard teaching hospital), Hak Soo Cho and John Frangioni of Harvard Medical School, Akira Tsuda of Harvard School of Public Health, Numpon Insin and Moungi Bawendi of Massachusetts Institute of Technology, Manuela Semmler-Behnke of the Helmholtz Center Munchen, Germany report details in the journal Nature Biotechnology.

Definitely small

Nanoparticles are defined as particles of a particular material that have diameters in the range of 1 to a few hundred billionths of a meter. This extremely small scale has led researchers to investigate their potential for many different technologies including powerful catalysts, sub-microscopic electronic components and targeted drug delivery that can pinpoint disease sites in the body more effectively than conventional therapeutic agents and could be applied to a wide range of diseases. The fact that nanoparticles are so new and that they might infiltrate biological tissues and ecosystems perhaps with relative ease means they have also become a focus of concern for the risks to health and the environment they might bring. Recent toxicology has already demonstrated that nanoparticles can reach deep into the alveolar region of the lungs and trigger a severe inflammatory response.

Frangioni and colleagues have focused on both the drug delivery potential and the possible effects of nanoparticles in airborne pollution in their research. "Nanoparticles hold promise as therapeutic agents for a number of diseases," explains Frangioni, who is co-senior author on the Nature Biotech paper and a medical doctor in the Division of Hematology/Oncology at BIDMC and Associate Professor of Medicine and of Radiology at Harvard Medical School (HMS). Frangioni's research group has specialized in the development of imaging systems and contrast agents for those systems. He points out that the anatomy of the lung, with its enormous surface area to volume ratio and minimal barriers it presents to accessing the body, makes it a potentially very useful target for nanoparticle drug delivery and also a vulnerable entry point for pollutants.

Nanoparticle fate

"We have been interested in the fate of small particles after they deposit deep in the gas exchange region of the lung," adds research scientist Tsuda. "Determining the physicochemical characteristics of inhaled nanoparticles on their ability to cross the alveolar epithelial surface is an important step in understanding the biological effects associated with exposure to these particles."

Frangioni and Choi had previously investigated the clearance of nanoparticles from the lungs and had characterised certain elements that regulate this process. "To be of value clinically, nanoparticles must be able to either biodegrade into biologically inert compounds, or be efficiently cleared from the body," says Choi, otherwise the accumulation of the therapeutic nanoparticles might have as yet unknown toxic effects.

The aim of this new study was to determine the characteristics and parameters of inhaled nanoparticles that mediate their uptake into the body -- from the external environment, across the alveolar lung surface and into the lymphatic system and bloodstream and eventually to other internal organs.

The researchers used their FLARE (fluorescence-assisted resection and exploration) imaging system, systematically varying the chemical composition, size, shape and surface charge of a group of near-infrared fluorescent nanoparticles to compare the behaviour of these particles. The team then tracked the particles movements within the lungs of a rat model over a period of sixty minutes. Results were corroborated by using conventional radioactive tracers.

A FLARE for pulmonary imaging

"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," explains Frangioni. The team's FLARE system has previously been used in image-guided cancer surgery as well as other applications.

The team established that non-positively charged nanoparticles of less than 34 nanometres diameter, appear within the lymph nodes that drain the lungs within half an hour. Much smaller nanoparticles of just 6 nm in diameter or less that carry both a positive and a separated negative charge, zwitterionic nanoparticles are much faster moving, reaching the draining lymph nodes within just a few minutes and then being cleared by the kidneys into urine.

"These new findings can be applied to design and optimize particles for drug delivery by inhalation therapy," Tsuda says. "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."

Frangioni adds that this present study complements the earlier work in which they defined the characteristics of nanoparticles that regulate efficient clearance from the body. "With these new findings, which define the characteristics that regulate uptake into the body, 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," he says.

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.