No abstract

The optimal threshold values that were determined represent a maximized test sensitivity and specificity and are not subject to any user bias. When applied to the datasets that we studied, our results suggest the use of patient specific QA as a safety tool that can effectively prevent large errors (e.g., σ > 3 mm) as opposed to a tool to improve the quality of IMRT delivery.

Polyethylene glycol (PEG) has promoted the prospective applications of nanoparticles (NPs) in cancer therapy. PEG is used to evade the immune system allowing NPs accumulation within the tumor using its leaky vasculature. However, the cellular uptake of PEG-coated (PEGylated) NPs is lower in comparison to non-PEGylated NPs since PEG minimizes surface binding of ligands that mediate NP endocytosis. For improved outcome in therapeutic applications, it is necessary to enhance the uptake of PEGylated NPs. We added a peptide containing an integrin binding domain known as the RGD sequence to the NP surface in addition to PEG. We used gold NPs (GNPs) of sizes 14, 50, and 70 nm in this study. Our in vitro data for HeLa cells show enhanced uptake for NPs coated with both PEG and the peptide in comparison to PEGylated GNPs. NPs of size 50 nm had the highest uptake among the three sizes for all GNP surfaces. A similar size-dependent trend was observed for MDA-MB-231 cells for as-made GNPs with lower uptake in comparison to HeLa cells. However, only 14 nm peptide-modified PEGylated NPs had enhanced uptake. Hence, NP uptake was found dependent on cell type and NP surface properties. A properly designed NP system with both PEG and cell membrane targeting peptides can be used to protect it from the immune system and promote internalization by cells upon entry into tumor environment.

To enhance PEG uptake for radiation therapy, a peptide containing an integrin binding domain (RGD) was conjugated to PEG. Nanoparticles functionalized with both the RGD peptide and PEG had a higher uptake than NPs functionalized with PEG alone.