A method for the efficient cellular uptake and retention of small modified gold nanoparticles for the radiosensitization of cells.

Unlabelled: 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.

From The Clinical Editor: In an effort to increase the radiosensitization of HeLa cells, his paper discusses a transient transfection-based method to enhance gold nanoparticle intracellular delivery.