RESUMO
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.
RESUMO
Gold nanocages have recently emerged as a novel class of photothermal transducers and drug carriers for cancer treatment. However, their pharmacokinetics and tumor targeting capability remain largely unexplored due to the lack of an imaging modality for quick and reliable mapping of their distributions in vivo. Herein, Au nanocages were prepared with controlled physicochemical properties and radiolabeled with (64)Cu in high specific activities for in vivo evaluation using positron emission tomography (PET). Our pharmacokinetic studies with femtomolar administrations suggest that 30 nm nanocages had a greatly improved biodistribution profile than 55 nm nanocages, together with higher blood retention and lower hepatic and splenic uptakes. In a murine EMT-6 breast cancer model, the small cages also showed a significantly higher level of tumor uptake and a greater tumor-to-muscle ratio than the large cages. Quantitative PET imaging confirmed rapid accumulation and retention of Au nanocages inside the tumors. The ability to directly and quickly image the distribution of Au nanocages in vivo allows us to further optimize their physicochemical properties for a range of theranostic applications.