(24c) Polyethylene Glycol (PEG) Stabilized Cisplatin-Tethered Gold Nanoparticle Platform for Drug Delivery: Understanding Engineered Surface and Drug Performance

Design of nanoparticle drug delivery platforms through surface functionalization to achieve desirable therapeutic performance is a major challenge. In this presentation, we report on polyethylene glycol (PEG) stabilized cisplatin-tethered gold nanoparticles (AuNPs) for antitumor drug delivery. Assessment of surface modification and its influence on drug loading and colloidal stability was conducted.  To fabricate surface functionalized Pt^II-AuNPs, a dendrimer-like ligand, a dendron, was used to load cisplatin onto the AuNP surface through metal-carboxylate coordination. The branched structure of the dendron enables high loading capacity with respect to Pt^II pharmacophores, while providing steric resistance to aggregation. We showed that steric hindrance provided satisfactory colloidal stability at relatively low Pt^II loading, but is insufficient at high Pt^II loading due to increased charge neutralization.

In this context, further surface modification by PEGylation of AuNP-dendron conjugates was conducted. For the formulation, thiolated PEG at different concentrations relative to the dendron and of different molar masses was examined. On a quantitative basis, the extent of PEGylation was characterized and its influence on cisplatin drug payload was examined using an electrospray differential mobility analyzer (ES-DMA) coupled to a quadrapole inductively coupled plasma mass spectrometer (ICP-MS). We demonstrated that PEGylated AuNP conjugates (AuNP-dendron-SH-PEG-Pt^II) exhibited enhanced dispersion stability compared with native AuNP-dendron-Pt^II due to additional steric stabilization arising from the attached PEG.  Overall, the loading capacity for Pt^II was improved, indicating insignificant displacement of the complexing dendron by the PEG ligand on the surface. This was further confirmed by attenuated total reflectance Fourier transform infrared spectral analysis of deposited films. The conjugation of cisplatin on the PEG-stabilized AuNP vector was demonstrated to be stable under biologically relevant conditions (e.g., high ionic strength). Finally, the pH dependent drug release performance was evaluated.