Journal
LANGMUIR
Volume 34, Issue 1, Pages 154-163Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.langmuir.7b02354
Keywords
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Funding
- U.S. Department of Commerce, National Institute of Standards and Technology [70NANB13H021]
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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 (<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.
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