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Cisplatin-complexed gold nanoparticles (Pt II -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 II -AuNP was synthesized as a model antitumor drug platform, where Pt II 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 II 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 (&lt;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 II loading was simultaneously quantified by determination of Pt mass. Colloidal stability was quantitatively evaluated in biologically relevant media. Finally, the pH-dependent Pt II release performance was evaluated. We observed 9% and 16% Pt II release at drug loadings of 0.5 and 1.9 Pt II /nm 2 , respectively. The relative molar mass of PEG had no significant influence on Pt II uptake or release performance, while PEGylation substantially improved the colloidal stability of the conjugate. Notably, the Pt II release over 10 days (examined at 0.5 Pt II /nm 2 drug loading) remained constant for non-PEGylated, 1K-PEGylated, and 5K-PEGylated conjugates.

Surface Modification of Cisplatin-Complexed Gold Nanoparticles and Its Influence on Colloidal Stability, Drug Loading, and Drug Release