In vivo tumor targeting and radionuclide imaging with self-assembled nanoparticles

In an attempt to determine what factors make one nanoparticle better than another at targeting tumors, a team of investigators in Korea have conducted a systematic tumor-targeting study of a variety of self-assembling nanoparticles.

The results of these experiments identified several factors that appear to play a major role in determining a given particle’s tumor-targeting characteristics.

Reporting its work in the journal Biomaterials, a research team headed by Sang Yoon Kim, Ph.D., of the University of Ulsan College of Medicine, in Seoul, focused on chemical constituents that would self-assemble into nanoparticles. The general strategy they followed was to attach various hydrophobic molecules – those that try to avoid water – to different types of hydrophilic, or water-seeking, polymers. In general, polymers that have both hydrophilic and hydrophobic components tend to associate with one another to create a structure that surrounds the hydrophobic regions with a hydrophilic shell.

To track the distribution of the various nanoparticles, the researchers labeled them with radioactive iodine-131 (131I). After determining that a given nanoparticle was stable in human plasma, the investigators then injected the labeled nanoparticles into tumor-bearing mice. Radiographic measurements showed that the nanoparticles displayed a wide range of pharmacokinetic and tumor-targeting properties. Among the most notable and unexpected findings were that most of the particles had relatively short lifetimes in the bloodstream, generally less than a few hours, and that many of the particles were less stable in the body than was expected based on their stability in serum.

As expected, those particles that were able to escape the leaky blood vessels surrounding tumors were better able to target tumors. So, too, were nanoparticles that were taken up rapidly by cells.

Of all the nanoparticles that the investigators created, one was vastly superior to all others at targeting tumors. This nanoparticle consisted of the polymer chitosan, obtained from crustacean shells, linked to the fluorescent dye molecule fluorescein isothiocyanate, also known as FITC. This nanoparticle, with an average diameter of 150 nanometers, had the longest lifetime in the bloodstream and clearly delineated tumors three days after injection. Electron microscopy studies of tumor tissue showed clearly that the nanoparticles not only surrounded malignant cells but that they had accumulated within the cells.

This work is detailed in a paper titled, “In vivo tumor targeting and radionuclide imaging with self-assembled nanoparticles: Mechanisms, key factors, and their implications.” Investigators from Hanyang University, Seoul National University, Kyungpook National University, and the Korea Institute of Science, all in the Republic of Korea, also participated in this study. This paper was published online in advance of print publication. An abstract of this paper is available through PubMed. View abstract.


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