Nucleic acid-directed self-assembly of multifunctional gold nanoparticle imaging agents

Abstract

Gold nanoparticles have attracted much interest as a platform for development of multifunctional imaging and therapeutic agents. Multifunctionalized gold nanoparticles are generally constructed by covalent assembly of a gold core with thiolated ligands. In this study, we have assembled multifunctionalized gold nanoparticles in one step by nucleic acid hybridization of ODN (oligodeoxynucleotide)-derivatized gold nanoparticles with a library of pre-functionalized complementary PNAs (peptide nucleic acids). The PNAs were functionalized by conjugation with DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) for chelating 64Cu for PET imaging, PEG (polyethylene glycol) for conferring stealth properties, and Cy5 for fluorescent imaging. The resulting nanoparticles showed good stability both in vitro and in vivo showing biodistribution behavior in a mouse that would be expected for a PEGylated gold nanoparticle rather than that for the radiolabelled PNA used in its assembly.

Facile synthesis, pharmacokinetic and systemic clearance evaluation, and positron emission tomography cancer imaging of64Cu–Au alloy nanoclusters

“…[23][24][25][26] Previously, we have reported the synthesis of 64 Cu alloyed AuNPs for cancer PET imaging and revealed improved radiolabel stability and diagnostic accuracy. [23][24][25][26] Previously, we have reported the synthesis of 64 Cu alloyed AuNPs for cancer PET imaging and revealed improved radiolabel stability and diagnostic accuracy.…”

Nanogels from Metal-Chelating Crosslinkers as Versatile Platforms Applied to Copper-64 PET Imaging of Tumors and Metastases

“…More impressively, this blood retention occurred without conjugation of PEG to the nanogels, which is routinely performed to increase blood circulation time in vivo . 16 , 24 , 49 - 52 …”

Positron emission tomography and nanotechnology: A dynamic duo for cancer theranostics

“…Xie et al first reported the biodistribution of Au nanoshell-coated silica cores, radiolabeled with 64 Cu via bifunctional chelating agent DOTA, in head and neck squamous cell carcinoma (HNSCC) xenograft-bearing rats. [192] In addition to nanoshells [193, 194], chelator-based PET studies have extensively been carried out for other AuNP morphologies like nanospheres [195–198], hollow nanospheres[199, 200], nanostars[180], nanocages[201], nanorods[202], nanotripods[203], nanodumbells [204], and ultrasmall nanoparticles [205, 206] (Figure 7a–f). In these studies, PET was successfully used to assess the biodistribution and tumor accumulation of radiolabeled nanoplatforms.…”