Source: Peiman Shahbeigi-Roodposhti and Sina Shahbazmohamadi, Biomedical Engineering Department, University of Connecticut, Storrs, Connecticut

Nanoparticles have been increasingly used research towards targeted drug delivery and controlled drug release. While most of these particles have been developed as polymeric or liposomal particles because of their biocompatibility, there is a trend in current research toward the use of metallic and magnetic nanoparticles. These metallic nanoparticles were originally used as a contrast agent in imaging, but recent advances have shown how important they could be in drug and gene delivery and in therapeutics. Gold, silver, and paramagnetic nanoparticles have the greatest share in research being done. They have been shown to have good biocompatibility and certain varieties of magnetic nanoparticles have already been developed and distributed as therapeutic targeted drugs.  

These heavy elements are typically imaged for research using fluorescence to evaluate delivery and distribution, but their atomic weights are good qualifications for increased contrast in backscatter electron analysis using a scanning electron microscope (SEM). Energy dispersive X-ray spectroscopy, which uses characteristic X-rays emitted upon electron beam interaction with the sample to identify chemical composition, can also be used with the SEM. These methods have the benefits of increased resolution and increased confidence in detection, as the EDS can ensure that the subject of an image is of the right composition, while current fluorescence methods can detach from the nanoparticles and can fade quickly while imaging. 

This demonstration will examine the size-dependent metal nanoparticle distribution in organs of the body over time. Excised organs will be examined with SEM for various sizes of particles at a range of time points after particle delivery to the body. 

1. Nanoparticle Injection and Organ Harvesting

1. Inject nanoparticles into an anesthetized mouse intravenously to allow passive targeting.
2. At the desired time points, i.e., 1, 4 and 8 weeks, post-injection, humanely euthanize the mice according to American Veterinary Medical Association (AVMA) Guidelines.
3. Open the body cavity and surgically remove the organs of interest. Place the organs in 10% phosphate buffered formalin in a polypropylene container until sample preparation.