Abstract
BackgroundGold nanoparticles (AuNPs) have shown great promise as scaffolds for gene therapy vectors due to their attractive physiochemical properties which include biocompatibility, ease of functionalization via the nearly covalent gold-sulfur dative bond, and surface plasmon optical properties. Previously, we synthesized stable AuNP-polyamidoamine (AuPAMAM) conjugates and showed their success in vitro as non-viral gene delivery vectors.ResultsIn this study, we systematically perturbed each component of the AuPAMAM conjugates and analyzed the resulting effect on transfection efficiency. Due to the modular, bottom-up nature of the AuPAMAM synthesis, we were able to probe each step of the fabrication process. The relationship between each conjugation parameter and the function of the final vector were investigated. More than fourfold enhanced transfection efficiency was achieved by modifying the PAMAM concentration, PAMAM core chemistry, PAMAM terminus chemistry, and self-assembled monolayer composition of the AuPAMAM conjugates.ConclusionsThis work suggest that AuPAMAM synthesis platform is a promising non-viral gene therapy approach and highlights the importance of inspecting the role of each individual constituent in all nanotechnology hybrid materials.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-016-0178-9) contains supplementary material, which is available to authorized users.
Highlights
Gold nanoparticles (AuNPs) have shown great promise as scaffolds for gene therapy vectors due to their attractive physiochemical properties which include biocompatibility, ease of functionalization via the nearly covalent gold-sulfur dative bond, and surface plasmon optical properties
Excess mercaptoundecanoic acid (MUA) was removed by three phosphate buffered saline (PBS) washes in a 10 kDa cutoff centrifuge filter
Once the MUA selfassembled monolayer (SAM) was formed on the gold nanoparticle (AuNP), the terminal carboxylic acid moiety of the MUA ligands was activated to bind the aminated dendrimers
Summary
Gold nanoparticles (AuNPs) have shown great promise as scaffolds for gene therapy vectors due to their attractive physiochemical properties which include biocompatibility, ease of functionalization via the nearly covalent gold-sulfur dative bond, and surface plasmon optical properties. Figueroa et al J Nanobiotechnol (2016) 14:24 cores by coating them with PAMAM dendrimers produces a hybrid material with novel properties that would not exist with either material alone [16, 19]. These novel properties are created by the physical and chemical interactions between the AuNP core and the dendritic shell. PAMAM dendrimers enhance cellular uptake and endosomal escape, while the AuNP core may reduce dendrimer cytotoxicity and allows ease of characterization by virtue of their optical plasmon properties [14, 16, 19,20,21,22]
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