title: Third generation gold nanoplatform optimized for radiation therapy.
abstract: We report the design and fabrication of third generation ultrasmall PEGylated gold nanoparticles based platform (AuRad™) optimized for applications in radiation therapy. The AuRad™nanoplatform has the following key features: (I) surface coating of hetero-bifunctional-PEG with amine, carboxyl, methoxy functional groups, which make this a versatile nanoplatform to conjugate various moieties like fluorophores, peptides, drugs, radiolabels; (II) size that is optimized for longer circulation, higher tumor uptake and modulated clearance; (III) high radiation enhancement. We have synthesized ultrasmall 2-3 nm gold nanoparticles, followed by attachment of hetero-bifunctional PEG and further conjugation of fluorophore AlexaFlour 647 for optical imaging, with a stability of more than 6 months. Confocal bioimaging with HeLa cells showed robust uptake of biocompatible nanoparticles in cells. Irradiation experiments X-rays showed greater than 2.8-fold cell kill enhancement as demonstrated by clonogenic survival assays. The results indicate that AuRad nanoplatform can act as potential theranostic agent in radiation therapy.
authors.affiliation: Electronic Materials Research Institute and Department of Physics, Northeastern University, Boston, MA, USA ; Department of Radiation Oncology, Dana Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Department of Radiation Oncology, Dana Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Houari
authors.initials: H
authors.lastname: Korideck
authors.affiliation: Department of Radiation Oncology, Dana Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Wilfred
authors.initials: W
authors.lastname: Ngwa
authors.affiliation: Department of Radiation Oncology, Dana Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Ross I
authors.initials: RI
authors.lastname: Berbeco
authors.affiliation: Department of Radiation Oncology, Dana Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: G Mike
authors.initials: GM
authors.lastname: Makrigiorgos
authors.affiliation: Electronic Materials Research Institute and Department of Physics, Northeastern University, Boston, MA, USA ; Department of Radiation Oncology, Dana Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Sridhar
keywords: Gold nanoparticles; PEGylation; clonogenic assay; multifunctional nanoparticles; radiation therapy