The Effect of Surface-Modified Gold Nanorods on the Early Stage of Embryonic Development and Angiogenesis: Insight into the Molecular Pathways

Abstract

Gold nanorods have been implicated in several biomedical applications. Herein, the effect of two surface-modified gold nanorods on the early stages of embryogenesis and angiogenesis was investigated using avian embryos at three days and their chorioallantoic membrane (CAM) at five days of incubation. We found that gold nanorods (GNR) modified with PEGylated phospholipid moiety show a high mortality rate in embryos after four days of exposure compared to GNR modified with PEGylated cholesterol moiety. Meanwhile, our data revealed that surface modified-GNR significantly inhibit the formation of new blood vessels in the treated CAM model after 48 h of exposure. Moreover, we report that surface-modified GNR significantly deregulate the expression of several genes implicated in cell proliferation, invasion, apoptosis, cellular energy metabolism, and angiogenesis. On the other hand, our data point out that GNR treatments can modulate the expression patterns of JNK1/2/3, NF-KB/p38, and MAPK, which could be the main molecular pathways of the nanorods in our experimental models.

Developmental Toxicity of Surface-Modified Gold Nanorods in the Zebrafish Model

“…AuNRs were successfully synthesized, functionalized with phospholipid, and characterized, as described previously. 19 UV–vis spectrophotometry demonstrated the typical longitudinal and transverse peaks of the golden nanorods (GNRs) at ∼523 nm and 760 nm, respectively, which suggest their excellent stability. The surface of nanorods was functionalized with a phospholipid moiety through S–Au linkage to eliminate the toxicity of cetyltrimethylammonium bromide (CTAB) and increase the colloidal stability of the nanorods.…”

“…However, their model. 18,19 Herein, we used the zebrafish embryos to provide insights into the impact of these AuNRs on the early stage of embryogenesis and their possible toxicity on the developing body systems, particularly the cardiac and neuromuscular systems.…”

“…AuNRs were successfully synthesized, functionalized with PEGylated phospholipid moiety and characterized, as described previously. 19 AuNRs were prepared using a mixture of CTAB (Sigma-Aldrich, USA) and sodium oleate (NaOL, Sigma-Aldrich, USA). Briefly, seed particles were synthesized by adding sodium borohydride (NaBH 4 , Sigma-Aldrich, USA) to a mixture of CTAB and chloroauric acid (HAuCl 4 , CTAB, Sigma-Aldrich, USA).…”

“… 17 Furthermore, they exhibited high cytotoxicity against a panel of breast cancer cell lines 18 and demonstrated anti-angiogenesis properties. 19 We demonstrated in our previous work that AuNRs conjugated with a phospholipid moiety modulated several apoptotic signaling pathways in breast cancer cells through activation of TNF and p53 signaling pathways, and other regulatory genes contributed to proapoptotic pathways and by suppression of antiapoptotic pathways. 20 In this study, we explored the toxicity of gold nanorods (AuNRs) modified with a phospholipid moiety on the normal embryonic development of zebrafish using organ-specific toxicity assays (cardiotoxicity and neurotoxicity) and apoptotic markers to further understand their mechanism of action and toxicity modality.…”

“…In our previous work, rod-shaped AuNP functionalized with polyethylene glycol (PEG)-phospholipid ligand demonstrated enhanced colloidal stability and increased transdermal delivery properties . Furthermore, they exhibited high cytotoxicity against a panel of breast cancer cell lines and demonstrated anti-angiogenesis properties . We demonstrated in our previous work that AuNRs conjugated with a phospholipid moiety modulated several apoptotic signaling pathways in breast cancer cells through activation of TNF and p53 signaling pathways, and other regulatory genes contributed to proapoptotic pathways and by suppression of antiapoptotic pathways .…”