Using a novel, real-time imaging system, scientists have tracked a group of near-infrared (NIR) fluorescent nanoparticles from the airspaces of the lungs, into the body and out again, providing a description of their characteristics and behavior, which could be used in developing therapeutic agents to treat pulmonary disease, as well as offering a greater understanding of the health effects of air pollution.
The aim of this 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 organs. To do this, the scientists made use of the FLARE (Fluorescence-Assisted Resection and Exploration) imaging system, systematically varying the chemical composition, size, shape and surface charge of a group of NIR fluorescent nanoparticles to compare the physiochemical properties of the various engineered particles. The investigators then tracked the movement of the varying nanoparticles in the lungs of rat models over a period of one hour, and also verified results using conventional radioactive tracers.
Led by investigators at Beth Israel Deaconess Medical Center (BIDMC) and the Harvard School of Public Health, the findings are described in the November 7 Advance Online issue of the journal Nature Biotechnology.
"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 co-senior author John V. Frangioni, MD, Ph.D., of the Division of Hematology/Oncology at BIDMC and Associate Professor of Medicine and of Radiology at Harvard Medical School (HMS), whose laboratory developed the FLARE system for use in image-guided cancer surgery as well as other applications, and specializes in the development of imaging systems and of contrast agent development for molecular imaging.
Their results established that non-positively charged nanoparticles, smaller than 34 nm in diameter, appeared in the lung-draining lymph nodes within 30 minutes. They also found that nanoparticles smaller than 6 nm in diameter with "zwitterionic" characteristics (equal positive and negative charge) traveled to the draining lymph nodes within just a few minutes, subsequently being cleared by the kidneys into urine.
"These new findings can be applied to design and optimize particles for drug delivery by inhalation therapy," notes Akira Tsuda, Ph.D., a research scientist in the Molecular and Integrative Physiological Sciences Program in the Department of Environmental Health at the Harvard School of Public Health. "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."
"This study complements our earlier work in which we defined the characteristics of nanoparticles that regulate efficient clearance from the body," adds Frangioni. "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."
Grants from the National Institutes of Health partially supported this work.
Source: Beth Israel Deaconess Medical Center
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Posted by Lee Mather
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