Abstract 4142: Surface engineering of quantum dots with multidentate polymer ligands: surface charge density affect on interactions at the nano-bio interface in vitro.
Authors: Sun Minghao , Jose Purnima , Yang Likun , Sundaresan Gobalakrishnan , Wang Li , Zweit Jamal 
Published: August 2014

Abstract
Nanomedicine is an emerging field with increasing applications in cancer diagnosis and therapy. However, these applications strongly depend on the nature of cellular and tissue interactions in vitro and in vivo, which in turn is strongly influenced by properties of nanomaterials. The effect of surface modification of nanoparticles on their interaction with biological compartments is not yet well understood. Here, a series of multidentate zwitterionic polymeric ligands were synthesized and applied to functionalize the surface of quantum dots (QDs), which have been extensively used for fluorescent imaging in vitro and in vivo. The structure of polymeric ligands was tuned by changing their composition, and QDs with different surface charge density were obtained using these polymers as coating ligands. Highly stable, compact and biocompatible hydrophilic QDs were obtained after ligand exchange and QDs were tuned to have zeta potentials from -25 mV to -55 mV. Compared with small zwitterionic ligand coated QDs, cell viability of multidentate zwitterionic polymer ligand coated QDs were improved due to their better bio-stability originating from the multiple chelation of polymer ligand with surface of nanoparticles. The interaction of QDs, having different surface charge density, with various tumor/normal cell lines (KB 3-1, KB 8-5, COLO 205, A-549, FaDu, SK-OV-3, and HEK-293) was investigated. The surface charge densities of the nanoparticles profoundly influence their interactions with most cells. High surface charge (-55 mV and -40 mV) density increased interaction of nanoparticles with some cell membranes of tumor cells such as COLO 205 and KB 3-1. However, other tumor cells showed less sensitivity to the surface charge density of nanoparticles and displayed reduced nonspecific binding (FaDu, A-549, and SK-OV-3). The normal prostate cell line HEK-293 showed lowest interaction with these zwitterionic QDs. The surface bioconjugation of QDs with folic acid increased the intracellular internalization of QDs in KB 3-1 cell lines (with high folate receptor expression) compared with COLO 205 cell lines (low folate receptor expression), most likely due to the folate receptor mediated endocytosis. From our initial investigations, the surface properties of nanoparticles influence the nature of their interactions at the cellular level. Such information could guide in vivo studies of these nanomaterials within an intact in vivo environment.
Citation Format: Minghao Sun, Purnima Jose, Likun Yang, Gobalakrishnan Sundaresan, Li Wang, Jamal Zweit. Surface engineering of quantum dots with multidentate polymer ligands: surface charge density affect on interactions at the nano-bio interface in vitro. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4142. doi:10.1158/1538-7445.AM2013-4142