Parallel multi-parameter study of PEI-functionalized gold nanoparticle synthesis for bio-medical applications: Part 1. A critical assessment of methodology, properties and stability
Tae Joon Cho, Justin M. Gorham, John M. Pettibone, Jingyu Liu, Jiaojie Tan, Vincent A. Hackley
Cationic polyethyleneimine (PEI) conjugated gold nanoparticles (AuNPs) that are chemically and physically stable under physiological conditions are an ideal candidate for certain bio-medical applications, in particular DNA transfection. However, the reproducibility of published methods to generate uniform stable species is problematic, as is the inadequate characterization of the resulting product under relevant conditions and over time. The principal objective of the present study was to develop an optimized and reproducible synthetic route for preparing stable PEI conjugated AuNPs (Au-PEIs). To achieve this objective, a parallel multi-parametric approach involving a total of 96 template studies evaluated the importance of 6 key factors: PEI molar mass, PEI structure, molar ratio of PEI/Au, concentration of reaction mixtures, reaction temperature and reaction time. Application of optimized conditions exhibited narrow size distributions with characteristic surface plasmon resonance absorption, and positive surface charge. The optimized Au-PEI product generated by this study exhibits exceptional stability under a broad range of representative physiological conditions, including isotonic media, pH and temperature variation, and the presence of proteins. Furthermore, the optimized Au-PEI product was highly reproducible and could be scaled in volume. Contributions from individual factors were elucidated using a broad and orthogonal characterization suite examining size and size distribution, optical absorbance, morphological transformation (agglomeration/aggregation), surface functionalities, and stability. Overall, this comprehensive multi-parametric investigation, supported by thorough characterization and rigorous testing, provides a robust foundation for the nanomedicine research community to benchmark response and potentially tailor for new applications.