Abstract
Cisplatin-complexed gold nanoparticles (Pt <sup>II</sup> -AuNP) provide a promising strategy for chemo-radiation-based anticancer drugs. Effective design of such platforms necessitates reliable assessment of surface engineering on a quantitative basis and its influence on drug payload, stability, and release. In this paper, poly(ethylene glycol) (PEG)-stabilized Pt <sup>II</sup> -AuNP was synthesized as a model antitumor drug platform, where Pt <sup>II</sup> is attached via a carboxyl-terminated dendron ligand. Surface modification by PEG and its influence on drug loading, colloidal stability, and drug release were assessed. Complexation with Pt <sup>II</sup> significantly degrades colloidal stability of the conjugate; however, PEGylation provides substantial improvement of stability in conjunction with an insignificant trade-off in drug loading capacity compared with the non-PEGylated control (<20% decrease in loading capacity). In this context, the effect of varying PEG concentration and molar mass was investigated. On a quantitative basis, the extent of PEGylation was characterized and its influence on dispersion stability and drug load was examined using electrospray differential mobility analysis (ES-DMA) hyphenated with inductively coupled plasma mass spectrometry (ICP-MS) and compared with attenuated total reflectance-FTIR. Using ES-DMA-ICP-MS, AuNP conjugates were size-classified based on their electrical mobility, while Pt <sup>II</sup> loading was simultaneously quantified by determination of Pt mass. Colloidal stability was quantitatively evaluated in biologically relevant media. Finally, the pH-dependent Pt <sup>II</sup> release performance was evaluated. We observed 9% and 16% Pt <sup>II</sup> release at drug loadings of 0.5 and 1.9 Pt <sup>II</sup> /nm <sup>2</sup> , respectively. The relative molar mass of PEG had no significant influence on Pt <sup>II</sup> uptake or release performance, while PEGylation substantially improved the colloidal stability of the conjugate. Notably, the Pt <sup>II</sup> release over 10 days (examined at 0.5 Pt <sup>II</sup> /nm <sup>2</sup> drug loading) remained constant for non-PEGylated, 1K-PEGylated, and 5K-PEGylated conjugates.