One Pot Synthesis of PEGylated Bimetallic Gold–Silver Nanoparticles for Imaging and Radiosensitization of Oral Cancers

Abstract

Background:Radiotherapy is an important treatment modality for many types of head and neck squamous cell carcinomas. Nanomaterials comprised of high atomic number (Z) elements are novel radiosensitizers enhance radiation injury by production of free radicals and subsequent DNA damage. Gold nanoparticles are upcoming as promising radiosensitizers due to their high (Z) biocompatibility, and ease for surface engineering. Bimetallic nanoparticles have shown enhanced anticancer activity compared to monometallic nanoparticles. Materials and Methods: PEG-coated Au-Ag alloy nanoparticles (BNPs) were synthesized using facile one pot synthesis techniques. Size of ~50±5nm measured by dynamic light scattering. Morphology, structural composition and elemental mapping were analyzed by electron microscopy and SAXS (small-angle X-ray scattering). The radiosensitization effects on KB oral cancer cells were evaluated by irradiation with 6MV X-rays on linear accelerator. Nuclear damage was imaged using confocal microscopy staining cells with Hoechst stain. Computed tomography (CT) contrast enhancement of BNPs was compared to that of the clinically used agent, Omnipaque. Results: BNPs were synthesized using PEG 600 as reducing and stabilizing agent. The surface charge of well dispersed colloidal BNPs solution was −5mV. Electron microscopy reveals spherical morphology. HAADF-STEM and elemental mapping studies showed that the constituent metals were Au and Ag intermixed nanoalloy. Hydrodynamic diameter was ~50±5nm due to PEG layer and water molecules absorption. SAXS measurement confirmed BNPs size around 35nm. Raman shift of around 20 cm −1 was observed when BNPs were coated with PEG. 1 H NMR showed extended involvement of − OH in synthesis. BNPs efficiently enter cytoplasm of KB cells and demonstrated potent in vitro radiosensitization with enhancement ratio ~1.5-1.7. Imaging Hoechst-stained nuclei demonstrated apoptosis in a dose-dependent manner. BNPs exhibit better CT contrast enhancement ability compared to Omnipaque. Conclusion: This bimetallic intermix nanoparticles could serve a dual function as radiosensitizer and CT contrast agent against oral cancers, and by extension possibly other cancers as well.

Bimetallic Gold/Silver and Bioactive Camptothecin Hybrid Nanoparticles for Eradication of Cancer Stem Cells in a Combination Manner

“…Quantitatively, Au–Ag/CPT/PDA NCs in the absence/presence of NIR lighting led to 39.73 and 43.65% reductions in surviving CSC spheroids, and relevant values from other groups were all below 16%. Previous research had proven that CSCs were more resistant to chemotherapeutic agents than bulk cancer cells but were sensitive to nanoparticle-mediated photothermal therapy …”

“…Previous research had proven that CSCs were more resistant to chemotherapeutic agents than bulk cancer cells but were sensitive to nanoparticle-mediated photothermal therapy. 41 It could be postulated that the combined effect from Au−Ag alloy NP decorated CPT NCs and their excellent photothermal performance led to the most potent inhibitory activity on CSC spheroids, in other words, the self-renewable behavior of CSCs. Possible acting mechanisms of Au−Ag/CPT/PDA NCs against CSCs were illuminated in Figure 8.…”

Improving the Effect of Cancer Cells Irradiation with X-rays and High-Energy Protons Using Bimetallic Palladium-Platinum Nanoparticles with Various Nanostructures

“…Analysis of cells apoptosis was performed by Annexin V-binding assay (Fluorescein isothiocyanate (FITC) Annexin V apoptosis detection Kit I (BD, Pharmingen, San Diego, CA, USA)), as described previously [ 20 ]. Cells were plated in a 24-well plate at a density of 10 6 /well.…”

“…Exemplary, the generation of ROS by cells under the influence of NPs has already been known in the literature, e.g., for the widely used gold nanoparticles [ 19 ]. There are also studies on the use of multicomponent metallic NPs for the improvement of radiotherapy effectiveness, such as gold-silver [ 20 ], gold-platinum, gold–palladium [ 21 ], gold-zinc [ 22 ] or gold-silver nanocomplexes [ 23 ]. The combined effect of metals was seen not only with respect to human cells but also in bacteria treated with bimetallic silver-zinc, silver-cobalt, silver-nickel or silver-copper NPs [ 24 ].…”

Synthesis and Properties of Ag‐Au Alloy Nanoparticles with Controlled Composition for Computed Tomography Imaging Applications

“…[12] Recent research has produced nanoparticles based on Au as an alternative for iodine complexes as a CT contrast agent. [13] The nano Au has a higher X-ray attenuation than iodine complexes due to its high atomic number (Z = 79) and high electron density. [14] The surface properties of the nano Au may be easily changed by biocompatible ligands, and it is also chemically inert and highly biocompatible.…”