Gold silver alloy nanoparticles (GSAN): an imaging probe for breast cancer screening with dual-energy mammography or computed tomography

Abstract

Earlier detection of breast cancer reduces mortality from this disease. As a result, the development of better screening techniques is a topic of intense interest. Contrast-enhanced dual-energy mammography (DEM) is a novel technique that has improved sensitivity for cancer detection. However, the development of contrast agents for this technique is in its infancy. We herein report gold-silver alloy nanoparticles (GSAN) that have potent DEM contrast properties and improved biocompatibility. GSAN formulations containing a range of gold:silver ratios and capped with m-PEG were synthesized and characterized using various analytical methods. DEM and computed tomography (CT) phantom imaging showed that GSAN produced robust contrast that was comparable to silver alone. Cell viability, reactive oxygen species generation and DNA damage results revealed that the formulations with 30% or higher gold content are cytocompatible to Hep G2 and J774A.1 cells. In vivo imaging was performed in mice with and without breast tumors. The results showed that GSAN produce strong DEM and CT contrast and accumulated in tumors. Furthermore, both in vivo imaging and ex vivo analysis indicated the excretion of GSAN via both urine and feces. In summary, GSAN produce strong DEM and CT contrast, and has potential for both blood pool imaging and for breast cancer screening.

Targeting integrins with RGD-conjugated gold nanoparticles in radiotherapy decreases the invasive activity of breast cancer cells

“…Fluorescein isothiocyanate-PEG-thiol, MW 5k (FITC-PEG-SH, substitution purity: .80%, "FITC-PEG-SH5k"), was purchased from Nanocs, Inc (New York, NY, USA). Cysteine-modified (RGD) 4 peptide (MW: 1,845.98, purity: .95%, abbreviated as "RGD peptide") with amino acid sequence RGDRGDRGDRGDPGC was purchased from RS synthesis, LLC (Louisville, KY, USA). Methoxy-PEG-SH5k, FITC-PEG-SH5k and RGD peptide were in powder form and dissolved in deionized (DI) water having an electric conductivity of ,0.1 μS/cm without further purification.…”

“…32 To target integrins with AuNPs and increase cellular uptake of AuNPs through the endocytosis of integrins, we conjugated RGD peptide to P-AuNPs (15 nm or 20 nm diameter). i-colloid Au was partially PEGylated (abbreviated as "P-AuNPs") and subsequently conjugated with cysteine-modified (RGD) 4 peptides (abbreviated as "RGD/P-AuNPs") ( Figure 1A). 26,27 A layer of PEG on the surface of AuNPs enhances stability under physiological conditions by providing a steric barrier as described previously.…”

“…3,4 As a high atomic number (Z) material, AuNPs can serve as sensitizers to enhance the effects of ionizing radiation (IR) through the photoelectric effect. 5 In recent studies, the size, shape and surface properties of nanoparticles were shown to improve the efficacy of tumor targeting 6,7 and enhance the effect of cancer therapy.…”

“…Endocytosis and recycling of integrins play essential roles in cancer cell migration and invasion. [22][23][24][25] In this study, we conjugated (RGD) 4 peptides on polyethylene glycolylated (PEGylated) AuNPs (P-AuNPs) to enable binding to integrins and internalization into cancer cells via endocytosis. We evaluated whether targeting integrins with RGD-conjugated P-AuNPs (RGD/P-AuNPs) could enhance radiation effects in cancer cells.…”

“…In contrast, other studies have revealed that AuNPs accumulated in endosomes or lysosomes. 4,[42][43][44][45] Ma et al 42 showed that AuNPs accumulate in the lysosomes in a size-dependent manner and impair the degradation capacity of lysosomes related to autophagy. Our results indicate that surface modification of P-AuNPs with RGD peptide plays an important role in efficient cellular internalization by the endocytotic pathway through integrins and accumulation in late endosomes and lysosomes.…”