(598a) Effects of Nanoparticle Surface Charge On Cellular Mechanisms of Internalization

Magnetic nanoparticles are the subject of intense research focusing on their synthesis, characterization, and functionalization. These magnetically responsive nanomaterials are attractive in various novel applications including: a) targeted drug delivery, b) MRI contrast enhancement agents, c) magnetic cell sorting schemes, d) nano-/bio-sensors, e) agents for cancer treatment, and f) magnetic assisted transfection. In order for many of these applications to be successful, the nanoparticle's physicochemical properties (e.g., shape, size, and surface chemistry) must be tailored to promote specific interactions between the cell and the nanoparticles. We have recently developed methods for the synthesis and modification of superparamagnetic iron-oxide nanoparticles with narrow size distributions. These magnetic nanoparticles have been functionalized with covalently-grafted fluorescent carboxymethyl-dextran (CMDx) chains with different degrees of COOH substitution. The varying degrees of COOH substitution in the CMDx chains have the effect of giving these nanoparticles different net surface charges, allowing us to systematically assess the effect of nanoparticle surface charge on nanoparticle/cell interactions. Through Confocal Microscopy and Inductively Coupled Plasma Mass Spectrometry, we have observed that more negatively charged nanoparticles have higher rates of cellular internalization than less negatively charged nanoparticles. We have also found, by inhibiting specific internalization pathways, that CMDx-coated nanoparticle internalization is mostly governed by (i) fluid-phase endocytosis, and (ii) receptor-mediated endocytosis due to non-specific protein/nanoparticle interactions. These findings and our on-going work can serve to guide design of nanoparticle surface coatings to control the extent and pathway of internalization in cells, enhancing the potential of magnetic nanoparticles in biomedical applications.