Modification of primary amines to higher order amines reduces in vivo hematological and immunotoxicity of cationic nanocarriers through TLR4 and complement pathways

Randall Toy; Pallab Pradhan; Vijayeetha Ramesh; Nelson C. Di Paolo; Blake Lash; Jiaying Liu; Emmeline L. Blanchard; Philip J. Santangelo; Dmitry M. Shayakhmetov; Krishnendu Roy

In vivo systemic toxicity induced by unmodified bPEI nanoparticles is dominated by a combination of changes in blood properties, stimulation of CXCL1 production in the spleen, and liver toxicity measured by increases in ALT levels in the serum (Fig. 6A) . To our knowledge, this is the first report identifying cationic polymer nanoparticle-induced changes to blood properties in vivo. We infer that the sharp increase in hematocrit after treatment with unmodified bPEI nanoparticles is associated with liver toxicity, as studies have correlated heightened levels of ALT to high hematocrit. [24, 42] IL-6 has been shown to increase production of acute phase proteins and CXCL1, which suggests that the All rights reserved. No reuse allowed without permission.