SCHEDULED MAINTENANCE
Optimization of PEG coated nanoscale gold particles for enhanced radiation therapy†
Abstract
Nanoscale gold particles are being used as a radiation dose enhancer in cancer research. The purpose of this study was to optimize the uptake of polyethylene glycol (PEG) functionalized gold nanoparticles (GNPs) for an enhanced therapeutic effect during radiation therapy. PEG is widely used in providing NPs with stealth properties, thus prolonging blood circulation times. However, PEG minimizes PEG-GNP interaction with cell surface ligands resulting in significantly lower in vitro cellular uptake. As intracellular localization of GNPs maximizes its therapeutic enhancement, there is a need to improve the uptake of PEG-GNPs. To enhance uptake, RGD peptide containing an integrin binding domain was conjugated along with PEG. Spherical GNPs of diameters 14 and 50 nm and PEG chain lengths of 2 kDa were used for the study. Nanoparticles functionalized with both RGD peptide and PEG had higher uptake than NPs functionalized with PEG alone. The enhancement in uptake was higher for 14 nm NPs as compared to 50 nm NPs. Our radiation therapy results showed that smaller NPs conjugated with PEG and RGD peptides have a three-fold therapeutic enhancement as compared to larger NPs in MDA-MB-231 cells at clinically relevant 6 MV energy. This study will shed light on clinical use of GNPs in radiation therapy in the near future.
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