Inhibition of Cancer Cell Migration by Gold Nanorods: Molecular Mechanisms and Implications for Cancer Therapy

Abstract

Gold nanorods have received much attention because of their distinct physicochemical properties and promising applications in bioimaging, biosensing, drug delivery, photothermal therapy, and optoelectronic devices. However, little is known regarding their effect on tumor metastasis. In the present investigation, serum protein‐coated gold nanorods (AuNRs) at low concentrations is shown to exhibit no apparent effects on the viability and proliferation of three different metastatic cancer cell lines, that is, MDA‐MB‐231 human breast cancer cells, PC3 human prostate cancer cells, and B16F10 mouse melanoma cells, but effectively inhibit their migration and invasion in vitro. Quantitative proteomics and real‐time PCR array analyses indicate that exposure of cells to AuNRs can down‐regulate the expression of diverse energy generation‐related genes, which accounts for their inhibition of mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis. The impairment of OXPHOS and glycolysis results in a distinctive reduction of ATP production and subsequent inhibition of F‐actin cytoskeletal assembly, which is crucial for the migration and invasion of cancer cells. The inhibitory effect of AuNRs on cancer cell migration is also confirmed in vivo. Taken together, the unique mechanism in inhibiting cancer cell migration by AuNRs might provide a new approach to specific cancer therapeutic treatment.

Targeting cancer cell integrins using gold nanorods in photothermal therapy inhibits migration through affecting cytoskeletal proteins

“…Herein, we reported that targeting AuNRs to cancer cell surface integrins could greatly rearrange the cytoskeleton proteins, thus enhancing the inhibition effect on cancer cell migration. Compared with nontargeted AuNRs, the integrin-targeted AuNRs are more effective on cell migration inhibition with a nanoparticle concentration at the nM scale (1,000× lower than the literature values) (18,19,22), which could be safer for future clinical use.…”

“…Due to their small size and surface modifications, nanoparticles, in general, are able to target tumors selectively (15) and have been widely used in cancer diagnosis and therapy (16,17). The recent discovery of nanoparticles' effect on inhibiting cancer cell migration or metastasis starts to draw the attention of researchers (18)(19)(20)(21)(22). However, high concentrations of nontargeted nanoparticles (in μM) were used in these previous studies, which might be an obstacle when considering the translation to clinical use.…”

“…Therefore, to maintain the nanoparticles' effect on impeding cancer cell migration, an intelligent design with a reduced quantity of nanoparticles promises to be crucial in the development of novel and effective antimetastasis therapy. In addition, the preliminary observations of several groups have shown that this inhibition effect of nanoparticles is related to some individual cytoskeleton proteins (18,19,22), such as microtubule and actin. However, various mechanisms have been proposed.…”

“…Soenen et al (19) reported that iron oxide nanoparticles at high concentrations within cells affect the cellular cytoskeleton and focal adhesion kinase. Zhou et al (22) showed gold nanorods (AuNRs) can inhibit ATP production and thus inhibit F-actin cytoskeletal assembly and decrease…”

Treatment of natural mammary gland tumors in canines and felines using gold nanorods-assisted plasmonic photothermal therapy to induce tumor apoptosis

“…[23][24][25] The second novelty was the optimization of AuNRs-PPTT's conditions to generate tumor apoptosis as a favorable cell death mechanism (rather than necrosis). 12,26,27 Herein, we directly injected the PEGylated AuNRs to the mammary tumors of each canine/feline as opposed to intravenous injection, as our previous study showed a better efficacy for intratumoral injection than intravenous injection, 1 although the latter could be helpful for some applications (especially for tumors that are not accessible for direct injection of AuNR). 8 We tested PPTT on canine and feline natural mammary gland tumors.…”