title: A method for the efficient cellular uptake and retention of small modified gold nanoparticles for the radiosensitization of cells.
abstract: Gold nanoparticles (GNP) enhance the absorbance of photons thereby increasing emission of Auger-/photoelectrons in the nm-μm range. Yet, a major disadvantage is their diameter-dependent cellular uptake with an optimum of ~50 nm which may not offer optimal radiosensitization. A method was developed to enhance the uptake of small GNP. GNP (10nm) were linked to DNA and transferred into HeLa cells by transient transfection (GNP-DT). Treatment of cells with GNP-DT resulted in a strong perinuclear focal accumulation, whereas this was dimmer and sparser for GNP-T (lacking DNA) and close to background levels in GNP-treated cells. Only GNP-DT showed a significant radiosensitizing effect (p=0.005) on clonogenic survival using clinically relevant megavolt x-rays. Our novel method markedly increases the uptake/retention and alters the localization of small GNP in cells compared to unmodified GNP. This work finally enables studying the radiosensitizing effects of differentially sized GNP.
  
  
  BACKGROUND
  In an effort to increase the radiosensitization of HeLa cells, his paper discusses a transient transfection-based method to enhance gold nanoparticle intracellular delivery.
authors.affiliation: Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Burger
authors.affiliation: Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Kirchhoff-Institut for Physics, University of Heidelberg, Heidelberg, Germany.
authors.forename: Abin
authors.initials: A
authors.lastname: Biswas
authors.affiliation: Cellnetworks Cluster and Institute for Physical Chemistry, Heidelberg University, Heidelberg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Barzan
authors.affiliation: Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Kirchner
authors.affiliation: Department of Anatomy and Developmental Biology, Center for Biomedicine and Medical Technology Mannheim (CBTM) Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Hiltraud
authors.initials: H
authors.lastname: Hosser
authors.affiliation: Kirchhoff-Institut for Physics, University of Heidelberg, Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hausmann
authors.affiliation: Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Kirchhoff-Institut for Physics, University of Heidelberg, Heidelberg, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Hildenbrand
authors.affiliation: Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Herskind
authors.affiliation: Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Frederik
authors.initials: F
authors.lastname: Wenz
authors.affiliation: Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. Electronic address: Marlon.Veldwijk@medma.uni-heidelberg.de.
authors.forename: Marlon R
authors.initials: MR
authors.lastname: Veldwijk
mesh_terms: D004247:DNA / Q000737:chemistry / Q000235:genetics; D006046:Gold / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D006367:HeLa Cells; D006801:Humans; D053768:Metal Nanoparticles / Q000008:administration & dosage*; D010316:Particle Size; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D014162:Transfection
chemical_list: D011838:Radiation-Sensitizing Agents; D006046:Gold; D004247:DNA
keywords: Auger electrons; Gold nanoparticles; Radiosensitization; Size dependency; Transfection; Uptake