Gold Nanoparticles Functionalized with Angiogenin for Wound Care Application

Abstract

In this work, we aimed to develop a hybrid theranostic nano-formulation based on gold nanoparticles (AuNP)—having a known anti-angiogenic character—and the angiogenin (ANG), in order to tune the angiogenesis-related phases involved in the multifaceted process of the wound healing. To this purpose, spherical were surface “decorated” with three variants of the protein, namely, the recombinant (rANG), the wild-type, physiologically present in the human plasma (wtANG) and a new mutant with a cysteine substitution of the serine at the residue 28 (S28CANG). The hybrid biointerface between AuNP and ANG was scrutinized by a multi-technique approach based on dynamic light scattering, spectroscopic (UV-visible, circular dichroism) and microscopic (atomic force and laser scanning confocal) techniques. The analyses of optical features of plasmonic gold nanoparticles allowed for discrimination of different adsorption modes—i.e.; predominant physisorption and/or chemisorption—triggered by the ANG primary sequence. Biophysical experiments with supported lipid bilayers (SLB), an artificial model of cell membrane, were performed by means of quartz crystal microbalance with dissipation monitoring acoustic sensing technique. Cellular experiments on human umbilical vein endothelial cells (HUVEC), in the absence or presence of copper—another co-player of angiogenesis—were carried out to assay the nanotoxicity of the hybrid protein-gold nanoassemblies as well as their effect on cell migration and tubulogenesis. Results pointed to the promising potential of these nanoplatforms, especially the new hybrid Au-S28CANG obtained with the covalent grafting of the mutant on the gold surface, for the modulation of angiogenesis processes in wound care.

Angiogenin and Copper Crossing in Wound Healing

“…The medical treatment of pathological angiogenesis as well as the modulation of physiological vessel growth, through the use of angiogenin or its peptide fragments, can be improved by using nanocarriers. Experiments carried out on endothelial cells revealed a significant improvement in wound closure and angiogenic activity after treatment with a multifunctional platform obtained by anchoring ANG to the surfaces of AuNPs [ 111 ]. Notably, this new hybrid nanoplatform triggers intracellular copper trafficking, confirming the correlation between metal and ANG in the angiogenic process.…”

Analysis of Nanotoxicity with Integrated Omics and Mechanobiology

“…Rapidly growing reports on breakthrough applications of NPs have allowed the recognition of their potential uses in biomedical fields [ 1 , 2 , 3 , 4 ]. NPs, which have at least one dimension of 100 nm or less, show modifications in the physiochemical properties depending on their size and large surface area to volume ratio as well as changes in the uptake levels and interactions with the human body through inhalation, penetration, and ingestion [ 1 , 5 ].…”

Peptides Derived from Angiogenin Regulate Cellular Copper Uptake

“…In endothelial cells, copper can induce ANG expression, affect the intracellular protein distribution and the signaling pathways [39]. Additionally, the copper binding to ANG has been found to increase the protein interaction [40], to modulate protein interaction with actin [41], and to induce pro-angiogenic activity both in differentiated neuroblastoma (SH-SY5Y line) [42] and endothelial (HUVEC line) [43] cells.…”