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Beyond platinum: synthesis, characterization, and in vitro toxicity of Cu(II)-releasing polymer nanoparticles for potential use as a drug delivery vector

Alesha N Harris, Barbara R Hinojosa, Montaleé D Chavious and Robby A Petros*

Author Affiliations

Department of Chemistry, University of North Texas, 1155 Union Circle, CB#305070, Denton, TX, 76203-5017, USA

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Nanoscale Research Letters 2011, 6:445  doi:10.1186/1556-276X-6-445

Published: 11 July 2011

Abstract

The field of drug delivery focuses primarily on delivering small organic molecules or DNA/RNA as therapeutics and has largely ignored the potential for delivering catalytically active transition metal ions and complexes. The delivery of a variety of transition metals has potential for inducing apoptosis in targeted cells. The chief aims of this work were the development of a suitable delivery vector for a prototypical transition metal, Cu2+, and demonstration of the ability to impact cancer cell viability via exposure to such a Cu-loaded vector. Carboxylate-functionalized nanoparticles were synthesized by free radical polymerization and were subsequently loaded with Cu2+ via binding to particle-bound carboxylate functional groups. Cu loading and release were characterized via ICP MS, EDX, XPS, and elemental analysis. Results demonstrated that Cu could be loaded in high weight percent (up to 16 wt.%) and that Cu was released from the particles in a pH-dependent manner. Metal release was a function of both pH and the presence of competing ligands. The toxicity of the particles was measured in HeLa cells where reductions in cell viability greater than 95% were observed at high Cu loading. The combined pH sensitivity and significant toxicity make this copper delivery vector an excellent candidate for the targeted killing of disease cells when combined with an effective cellular targeting strategy.

Keywords:
copper; polymer nanoparticles; copper ion release; drug delivery; oxidative stress; HeLa cells