Gold nanoparticles will block the blood supply to the tumor
A new direction in cancer nanotherapy: gold nanoparticles destroy the cells of the vessels feeding the tumorNanonewsnet based on University of Southampton materials: Gold nanoparticles bring scientists closer to a treatment for cancer
Scientists from the University of Southampton have developed "smart" nanomaterials that disrupt the blood supply to cancerous tumors.
A group of researchers led by physics professor Dr. Antonios Kanaras has shown that a small dose of gold nanoparticles can activate or suppress genes involved in angiogenesis – a complex process responsible for the delivery of oxygen and nutrients to most types of malignant tumors.
"The gold nanoparticles synthesized by us, functionalized with peptides, very effectively either activate or inhibit angiogenesis genes," Dr. Kanaras comments on his work.
But scientists have gone a step further. Laser-induced methods based on the principle of surface plasmon resonance of nanoparticles have already been presented as an effective therapeutic tool for the destruction of tumor cells. Dr. Kanaras and his colleagues applied a method based on low–intensity laser radiation to damage and restore a vital category of non-cancerous cells - human vascular endothelial cells. Endothelial cells form the inner lining of blood vessels and play a key role in angiogenesis.
Schematic representation of various types of gold nanoparticles used in the experiments of the Kanaras group.
NR – nanorods, HG – hollow nanoparticles, SP – spherical nanoparticles,
CS – nanoparticles with a silicon core and a shell of gold.
(fig. University of Southampton)
Experiments have shown that the degree of damage or recovery of these cells depends on the type of gold nanoparticles, which either target the cell membrane or are absorbed by the cell by endocytosis. Colloidal gold nanoparticles with the same electric charge and size, but carrying different peptide sequences, can selectively and purposefully include specific cellular functions associated with the growth of blood vessels. Scientists have managed to achieve specific binding of peptide-carrying nanoparticles with two endothelial cell-expressed receptors (VEGFR-1, NRP-1) controlling angiogenesis.
"We found that gold nanoparticles can play a dual role in manipulations with the cell. Using laser radiation, we can use nanoparticles either to destroy endothelial cells, thereby limiting blood flow to the tumor, or to selectively open the cell membrane and effectively deliver a drug to the cell," explains Dr. Kanaras.
Irradiation of gold nanoparticles with a laser leads to the occurrence of a phenomenon known as surface plasmon resonance (surface plasmon resonance). The membrane of human endothelial cells expresses the vascular endothelial growth factor receptor – VEGF (vascular endothelial growth factor). Under the influence of low-intensity laser irradiation, gold nanoparticles with a protective shell of oligoethylene glycol (OEG), functionalized with peptides specific to VEGF receptors, selectively open the membrane of the endothelial cell (upper row). Nanoparticles with an oligoethylene glycol shell that do not carry specific ligands on their surface are absorbed by the cell by endocytosis, leading to its destruction. (bottom row). (fig. Nano Letters)
Having tracked the intracellular fate of functional nanoparticles and the effect of nanoparticles with different peptide coatings on the expression profile of genes associated with hypoxia and angiogenesis, the scientists were convinced of the pronounced effect of their method on the expression of genes important for angiogenesis.
According to Dr. Kanaras and his colleagues, their treatment method based on soft laser irradiation mediated by plasmon, combined with specific targeting of cell membranes, opens up new ways to control cell permeability and represents a new strategy for gene regulation in endothelial cells.
The researchers consider their ultimate goal to be the development of a complete nanotechnological set of tools for influencing the process of angiogenesis. They have already passed about half of the way and, in order to put their plans into practice within five to ten years, they continue to actively search for sources of financing.
The results of the work have been published in the journals NanoLetters (Laser-Induced Damage and Recovery of Plasmonically Targeted Human Endothelial Cells) and Small (Receptor-Mediated Interactions between Colloidal Gold Nanoparticles and Human Umbilical Vein Endothelial Cells).
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