title: Systematically probing the bottom-up synthesis of AuPAMAM conjugates for enhanced transfection efficiency.
abstract: BACKGROUND
  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. Previously, we synthesized stable AuNP-polyamidoamine (AuPAMAM) conjugates and showed their success in vitro as non-viral gene delivery vectors.
  
  
  RESULTS
  In 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.
  
  
  CONCLUSIONS
  This 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.
authors.affiliation: Department of Bioengineering, Rice University, 6500 Main St, MS 142, Houston, 77030, TX, USA.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Figueroa
authors.affiliation: Department of Bioengineering, Rice University, 6500 Main St, MS 142, Houston, 77030, TX, USA.
authors.forename: J Stephen
authors.initials: JS
authors.lastname: Yan
authors.affiliation: Department of Bioengineering, Rice University, 6500 Main St, MS 142, Houston, 77030, TX, USA.
authors.forename: Nicolette K
authors.initials: NK
authors.lastname: Chamberlain-Simon
authors.affiliation: Department of Bioengineering, Rice University, 6500 Main St, MS 142, Houston, 77030, TX, USA.
authors.forename: Adam Y
authors.initials: AY
authors.lastname: Lin
authors.affiliation: Bellicum Pharmaceuticals, 2130 W Holcombe Blvd #850, Houston, 77030, TX, USA.
authors.forename: Aaron E
authors.initials: AE
authors.lastname: Foster
authors.affiliation: Department of Bioengineering, Rice University, 6500 Main St, MS 142, Houston, 77030, TX, USA. drezek@rice.edu.
authors.forename: Rebekah A
authors.initials: RA
authors.lastname: Drezek
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry; D050091:Dendrimers / Q000737:chemistry*; D006046:Gold / Q000737:chemistry*; D053768:Metal Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods; D013499:Surface Properties; D014162:Transfection / Q000379:methods
chemical_list: D001672:Biocompatible Materials; D050091:Dendrimers; C104700:PAMAM Starburst; D006046:Gold
keywords: Gene therapy; Nanoparticle; Nanotechnology