<p>Ag/Au Bimetallic Nanoparticles Inhibit Tumor Growth and Prevent Metastasis in a Mouse Model</p>

Abstract

Purpose: To evaluate the antitumor efficacy of Ag 3 Au 1 Trp 1:2 NPs in a SCID mouse cancer model, with respect to their effect on tumor growth, on tumor's metastatic potential and the underlying molecular mechanism. Subjects and Methods: Ag 3 Au 1 Trp 1:2 NPs were radiolabeled with Gallium-68 and the biodistribution was studied in Swiss mice without tumors and in SCID mice bearing tumors. SCID mice received intratumoral Ag 3 Au 1 Trp 1:2 NPs and tumor size was measured using calipers. Lung and liver tissues were extracted and studied microscopically for the detection of any metastatic sites. Changes in the Caspase-3 and TNF-related apoptosis-inducing ligand (TRAIL) were also investigated using real-time PCR and Western blot techniques, respectively. Results: In the 4T1 tumor-bearing SCID mice, Ag 3 Au 1 Trp 1:2 NPs showed quick passive accumulation at tumor sites at 30 mins post-injection. Mice that received the highest dose of NPs (5.6mg/mL) demonstrated a 1.9-fold lower tumor volume compared to that of the control group at 11 days post-injection, while mice that did not receive NPs showed metastatic sites in liver and lung. Extracted tumor tissue of treated mice revealed increased Casp-3 mRNA levels as well as elevated TRAIL protein levels. Conclusion: Based on our results, Ag 3 Au 1 Trp 1:2 NPs express anti-tumor and anti-metastatic effects in vivo. Ag 3 Au 1 Trp 1:2 NPs also reach tumor site via the enhancement and retention effect which results in the apoptotic death of cancerous cells selectively via the extrinsic TRAIL-dependent pathway.

The past, present, and future of breast cancer models for nanomedicine development

“… Poor radiation tolerance. Ag/Au bimetallic nanoparticles [168] NOD-SCID Lacks mature B and T cells. Reduced innate immunity.…”

Functionalized Nanoparticles Targeting Tumor-Associated Macrophages as Cancer Therapy

“…In vivo, NPs need to overcome many physiological barriers, including clearance by immune cells in the liver and spleen, various endothelial membranes, interstitial spaces, the plasma membrane, endosomal/lysosomal membranes and finally the nuclear membrane and pore complex [ 203 ]. Upon intravenous injection, a fraction of NPs reaches the TME primarily via the EPR effect, while another part is taken up by the macrophages of the liver and spleen, which are in direct contact with the bloodstream [ 204 , 205 ]. In addition, the abnormal structure of blood vessels in tumors allows the penetration of NPs, while defects in the lymphatic system facilitate the retention of NPs in the TME, where they slowly release their payload, such as antitumor drugs [ 206 , 207 ].…”

Green synthesis of biocompatible core–shell (Au–Ag) and hybrid (Au–ZnO and Ag–ZnO) bimetallic nanoparticles and evaluation of their potential antibacterial, antidiabetic, antiglycation and anticancer activities

“…Here we can state that Au based bimetallic NPs show better cytotoxic properties due to their excellent optical features and biochemical consistency thereby enhancing the properties as bimetallic NPs. Katifelis et al 92 reported that bimetallic Au–Ag alloy synthesized via chemical reduction activated caspase cascade in mice with tumor.…”

“…10 nm) are said to coat plasma membrane prior to their incorporation whereas larger NPs (100 nm) are directly internalized without accumulating onto cell membrane. 92 The major endocytosis mechanisms for NPs uptake are phagocytosis, diffusion, pinocytosis and clathrin/caveolae-mediated endocytosis. 97 Factors such as NPs size, morphology, surface chemistry and incubation environment affect the uptake and internalization of NPs.…”