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

Nouf N Mahmoud,Ishita Gupta,Hadeel Kheraldine,Ala-Eddin Al Moustafa,Semir Vranic,Maha Al-Asmakh,Zain Zaki Zakaria

doi:10.3390/ijms222011036

Nouf N Mahmoud, Ishita Gupta + Show 5 more

Open Access

https://doi.org/10.3390/ijms222011036

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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.

Highlights

Embryogenesis, a regulated embryonic development, shares remarkable cellular and molecular similarities with cancer, in cellular proliferation, cell differentiation/dedifferentiation, cell migration/invasion, and angiogenesis [1,2]
Dysregulated angiogenesis is correlated with several diseases caused or exacerbated by pathological angiogenesis [3]; for example, tumor angiogenesis plays a crucial role in cancer progression where cell invasion, metastasis, and excessive cancer cell growth are initiated or accelerated [4]
gold nanoparticles (GNP) and non-spherical types such as gold nanorods (GNR) are frequently utilized in biGNP and non-spherical types such as GNR are frequently utilized in omedical applications due to their unique features related to their particle size, surface biomedical applications due to their unique features related to their particle size, surface chemistry, and plasmonic properties [33]

Summary

Introduction

Embryogenesis, a regulated embryonic development, shares remarkable cellular and molecular similarities with cancer, in cellular proliferation, cell differentiation/dedifferentiation, cell migration/invasion, and angiogenesis [1,2]. Multiple key signaling pathways involved in embryonic development are often dysregulated in cancer, promoting tumor progression [2]. Various anti-angiogenesis drugs have been approved for cancer therapy by targeting different pro-angiogenetic regulatory factors and other pathways [8]; challenges including drug resistance and severe adverse effects may limit their clinical applications [9]. GNP has been utilized as angiogenesis modulators in multiple studies, and the activation or inhibition of angiogenesis by GNP is strongly correlated with their surface functionalization and formulation. The angiogenesis modulation activity of GNP was demonstrated in several in vivo and ex-vivo models; for example, GNP showed an anti-angiogenesis effect in a mouse model inoculated with human colorectal cancer [14], in an animal model of melanoma [15], and a mouse model of ovarian tumor [16]

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