Inhibition of tumor growth and metastasis by a self-therapeutic nanoparticle

Abstract

Although biomedical applications of nanotechnology, which typically involve functionalized nanoparticles, have taken significant strides, biological characterization of unmodified nanoparticles remains underinvestigated. Herein we demonstrate that unmodified gold nanoparticles (AuNPs) inhibit the proliferation of cancer cells in a size-and concentration-dependent manner by abrogating MAPK-signaling. In addition, these AuNPs reverse epithelial-mesenchymal transition (EMT) in cancer cells by reducing secretion of a number of proteins involved in EMT, up-regulating E-Cadherin, and down-regulating Snail, N-Cadherin, and Vimentin. Inhibition of MAPK signaling and reversal of EMT upon AuNP treatment inhibits tumor growth and metastasis in two separate orthotopic models of ovarian cancer. Western blot analyses of tumor tissues reveal up-regulation of E-Cadherin and down-regulation of Snail and phospho-MAPK, confirming the reversal of EMT and inhibition of MAPK signaling upon AuNP treatment. The ability of a single selftherapeutic nanoparticle to abrogate signaling cascades of multiple growth factors is distinctive and purports possible medical applications as potential antitumor and antimetastatic agent.drug delivery | heparin-binding growth factors

Differential cytotoxic and radiosensitizing effects of silver nanoparticles on triple-negative breast cancer and non-triple-negative breast cells

“…The ability to control the unique toxicity profiles of different nanomaterials will allow us to exploit specific vulnerabilities in cancer cells in a highly selective manner. 20,21 In support of this concept, recent studies have shown that gold nanoparticles alone can inhibit ovarian tumor growth and metastasis in mice. 21 Additionally, several groups showed that AgNPs have anti-breast cancer activity, [5][6][7] but concerns over the safety profile of AgNPs have limited their clinical translation.…”

“…However, the unique toxicity profiles of nanoparticles may also offer an opportunity to exploit specific vulnerabilities in cancer, provided that an appropriate disease target could be identified. 20,21 In this case, the nanomaterial itself would act as the therapeutic agent. Exposure of cells to AgNPs has been reported to cause DNA damage and induce oxidative stress, 22,23 and cells deficient in their capacity to repair DNA damage are and resistance to established therapies and dose-limiting toxic side effects frequently occur, new therapeutic agents are needed.…”

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

“…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.…”

Real-time cellular and molecular dynamics of bi-metallic self-therapeutic nanoparticle in cancer cells

“…Although cancer treatment strategies using functionalized nanoparticles have been significantly studied, the effect of un-modified bi-metallic nanoparticles remains under investigated (Arvizo et al 2013). Nanoparticles have been considered as the most prominent vehicle for targeted drugdelivery in cancer cells due to their unique properties of passing the biological barriers and distribution within the cellular counterparts through receptor-mediated or energydependent pathways (Bhattacharya and Mukherjee 2008).…”