Miktoarm star conjugated multifunctional gold nanoshells: synthesis and an evaluation of biocompatibility and cellular uptake

Abstract

A simple and highly versatile click chemistry based synthetic strategy to develop an ABC type miktoarm star ligand that is conjugated to gold nanoshells (GNS) is reported. The surface functionalized multifunctional GNS contain lipoic acid (LA) as a model therapeutic agent, poly(ethylene glycol) (PEG₃₅₀) as a solubilizing and stealth agent, and tetraethylene glycol (TEG) with a terminally conjugated thiol moiety. These GNS have an average size of 40 nm, a shell thickness of 6 nm, a well-defined crystal structure lattice (111), and a surface absorption plasmon band in the near infrared (NIR) region. The miktoarm star and GNS functionalized with this ligand are non-cytotoxic for up to 5 μg mL⁻¹ concentrations, and human umbilical vein endothelial cells internalize more than 85% of these GNS at 5 μg mL⁻¹. Our results establish that the biocompatible miktoarm star ligand provides a useful platform to synthetically articulate the introduction of multiple functions onto GNS, and enhance their scope by combining their inherent imaging capabilities with efficient delivery and accumulation of active therapeutic agents.