Surface Modification of Cisplatin-complexed Gold Nanoparticles and its Influence on Colloidal Stability Drug Loading and Release

摘要

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, polyethylene glycol (PEG) stabilized Pt^II-AuNP was synthesized as a model anti-tumor 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 (< 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 Pt^IIm² and 1.9 Pt^IIm², 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^IIm² drug loading) remained constant for non-PEGylated, 1K-PEGylated and 5K-PEGylated conjugates.