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Surface Modification of Cisplatin-complexed Gold Nanoparticles and its Influence on Colloidal Stability, Drug Loading and Release
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....
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Published in: | Langmuir 2017-12, Vol.34 (1), p.154-163 |
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Main Authors: | , , , , , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
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Summary: | 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
II
/nm
2
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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ISSN: | 0743-7463 1520-5827 |
DOI: | 10.1021/acs.langmuir.7b02354 |