Biologically Inspired Stealth Peptide-Capped Gold Nanoparticles

Introduction into the human body makes most nanoparticle systems susceptible to aggregation via nonspecific protein binding. Here, we developed a peptide-capped gold nanoparticle platform that withstands aggregation in undiluted human serum at 37 °C for 24 h. This biocompatible and natural system is...

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Bibliographic Details
Published in:Langmuir 2014-02, Vol.30 (7), p.1864-1870
Main Authors: Nowinski, Ann K, White, Andrew D, Keefe, Andrew J, Jiang, Shaoyi
Format: Article
Language:English
Subjects:
Animals
Biocompatible Materials - chemistry
Biocompatible Materials - pharmacokinetics
Cell Line
Cell Survival
Gold - blood
Gold - chemistry
Gold - pharmacokinetics
Humans
Metal Nanoparticles - chemistry
Mice
Models, Molecular
Molecular Structure
Peptides - blood
Peptides - chemistry
Peptides - pharmacokinetics
Surface Properties
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Summary:Introduction into the human body makes most nanoparticle systems susceptible to aggregation via nonspecific protein binding. Here, we developed a peptide-capped gold nanoparticle platform that withstands aggregation in undiluted human serum at 37 °C for 24 h. This biocompatible and natural system is based on mimicking human proteins which are enriched in negatively charged glutamic acid and positively charged lysine residues on their surface. The multifunctional EKEKEKE-PPPPC-Am peptide sequence consists of a stealth glutamic acid/lysine portion combined with a surface anchoring linker containing four prolines and a cysteine. Particle stability was measured via optical spectroscopy and dynamic light scattering in single protein, high salt, and undiluted human serum solutions. In vitro cell experiments demonstrate EKEKEKE-PPPPC-Am capped gold nanoparticles effectively minimize nonspecific cell uptake by nonphagocytic bovine aortic endothelial cells and phagocytic murine macrophage RAW 264.7 cells. Cytotoxicity studies show that peptide-capped gold nanoparticles do not affect cell viability. Finally, the peptide EKEKEKE-PPPPC-Am was extended with cyclic RGD to demonstrate specific cell targeting and stealth without using poly(ethylene glycol). Adding the functional peptide via peptide sequence extension avoids complex conjugation chemistries that are used for connection to synthetic materials. Inductively coupled plasma mass spectroscopy results indicate high aortic bovine endothelial cell uptake of c[RGDfE(SGG-KEKEKE-PPPPC-Am)] capped gold nanoparticles and low uptake of the control scrambled sequence c[RDGfE(SGG-KEKEKE-PPPPC-Am)] capped gold nanoparticles.
ISSN:0743-7463
1520-5827
DOI:10.1021/la404980g