Ligand-functionalized gold nanorods as theragnostic agents

摘要

Plasmon-resonant gold nanorods have been examined as multifunctional agents for imaging and photoactivated therapies. Au nanorods can be imaged with single-particle sensitivity by two-photon luminescence (TPL) when excited by pulsed NIR laser irradiation, and have been detected in vivo while passing through blood vessels at subpicomolar concentrations. TPL imaging can also be used to characterize the targeted delivery of ligand-functionalized nanorods to tumor cells. Nanorods were coated with oligoethyleneglycol (OEG) units using in situ dithiocarbamate formation, a novel and robust method of surface functionalization. Nanorods coated with OEG were shielded from nonspecific cell uptake, whereas those functionalized with folate-terminated OEG chains accumulated on the surface of tumor cells expressing their cognate receptor. Cells labeled with folate-conjugated nanorods can mediate photothermal effects when irradiated at NIR wavelengths, often resulting in a dramatic blebbing of the cell membrane, which was determined to be caused indirectly by the influx of extracellular Ca²⁺ following perforation of the cell membrane. With respect to preclinical testing, a protocol has been developed for the exhaustive removal of CTAB, a cytotoxic surfactant used in nanorod synthesis. Treatment with polystyrenesulfonate can yield “CTAB-free” nanorods with negligible toxicity.