Polyethylene Glycol (PEG) stabilized cisplatin-tethered gold nanoparticle platform for drug delivery: understanding engineered surface and drug performance by hyphenated ES-DMA with ICP-MS

J. Tan, T.J. Cho, D-H. Tsai, J. Liu, V.A. Hackley, M.R. Zachariah
University of Maryland College Park, US

Keywords: cisplatin-tethered gold nanoparticle, polyethylene glycol stabilization, anti-cancer drug delivery, drug loading and stability

Summary:

The cisplatin-complexed gold nanoparticle (PtII-AuNP) vector provides promising strategy for cancer treatment. Accurate engineering of such platform necessitates reliable assessment on a quantitative basis of surface modification, and its influence on drug payload and stability. In this study, polyethylene glycol (PEG) stabilized cisplatin-complexed gold nanoparticles were synthesized as anti-cancer drug platform where cisplatin (PtII) was tethered to a gold nanoparticle surface through dendrimer-like ligand; a so called dendron (Fig. 1). We showed that upon complexation of cisplatin, that colloidal stability decreased accordingly and the PEGylated gold nanoparticle conjugates (AuNP-dendron-SH-PEG-PtII) exhibited enhanced dispersion stability compared with bare AuNP-dendron-PtII (Fig. 2) with insignificant trade-off in drug dose. In this context, PEGs of different concentrations and of various molecular weights were used. On a quantitative basis, the extent of PEGylation was characterized and its influence on cisplatin drug payload was examined accordingly by hyphenated Electrospray Differential Mobility Analyzer (ES-DMA) with Inductively Coupled Plasma Mass Spectrometry (ICP-MS) (Fig. 3). By coupling ES-DMA with ICP-MS, gold nanoparticle conjugates were differentiated based on electrical mobility by ES-DMA and its cisplatin loading was quantified simultaneously through downstream ICP-MS. Finally, the conjugation of cisplatin was demonstrated to be stable under harsh environment: e.g. high ionic strength.