Authors: M.K. Khan, M.S.T. Kariapper, V. Kasturirangan, W. Lesniak, M. Sharma, H. Baumann, L.P. Balogh
Affilation: Translational Research Scientist, United States
Pages: 547 - 548
Keywords: PAMAM denrimer, nanodevice, inflammation, toxicity
Poly(amidoamine) (PAMAM) based dendrimers are a class of organic particulate nanomaterials with great promise for improvement in cancer imaging and therapy. In this study, we systematically modify terminal groups of the parent generation 5 primary amine terminated dendrimer to explore the biologic effects on toxicity and importantly also on inflammation in primary isolates of human lung cells. Primary amine groups of the parent dendrimers are eliminated sequentially by acetylation, thereby modulating the surface charge of the nanoparticles developed ranging from fully positive to neutral. Detailed quantitative measurements are taken of cellular toxicity and inflammation using primary human lung macrophages. The parent dendrimer with 119 amino terminals (surface positively charged) was toxic to the cells at or above 1 uM levels. At or below 0.1 uM level, this material did not exhibit any significant toxicity toward human lung macrophages. With progressive transformation of amino groups in to acetamide termini, the cytotoxic effects of PAMAM nanoparticles decreased. Acetylation of 77 amine termini (out 119) rendered the dendrimer nontoxic even when applied at a dose as high as 10 uM. Next, Inflammation was examined. None of the materials showed any significant irritant activity (causing induction of the human primary macrophages to express of inflammatory mediators). These macrophages were isolated from patients and directly tested in our assay system.