A new word in drug delivery and gene therapy: DNXomes
DNXomes – new multifunctional nanoparticles made of synthetic DNA
for the delivery of drugs and RNA to cells
NanoNewsNet based on materials from Cornell University:
'DNAsomes' can deliver multiple drugs or genetic therapy
Cornell University scientists have created multifunctional nanoparticles capable of simultaneously delivering several drugs and molecules to cells to suppress gene expression – small interfering RNAs. The particles are called DNXOMES because their building blocks are short strands of synthetic DNA.
Professor of biological and Environmental Engineering Dan Luo and his colleagues report their work in the journal Small (DNAsomes: Multifunctional DNA-Based Nanocarriers).
DNXomes can carry various drugs, as well as RNA molecules designed to specifically suppress gene expression. Their efficiency is significantly higher than that of delivery systems such as liposomes (tiny "wrappers" of phospholipid molecules that make up natural cell membranes) or polymer nanoparticles. In addition, DNXomes are less toxic to cells.
At the place of its natural residence – in the cell nucleus – DNA is a long molecular chains, complementary to each other along the entire length. Connecting, they form the famous double helix. Professor Lo's group creates short chains of synthetic DNA that connect to each other only by certain complementary sites and form Y-shaped structures as a result.
A lipid molecule is attached to the "tail" of the Y-block, and the drugs that need to be delivered to the cell are chemically bound to its "hands". If the purpose of the DNXOME is to suppress gene expression by small interfering RNA (miRNA) molecules (siRNA, small interfering RNA), synthetic DNA can carry a site complementary to this RNA, which will allow the RNA to easily join it. Delivery of miRNA to the cell nucleus, by the way, is a particularly difficult task for almost all delivery systems.
Such Y-structures, each of which consists of three DNA strands, were used by scientists as building blocks for their DNCs. In an aqueous solution, the combination of hydrophilic DNA with hydrophobic lipids causes Y-blocks to assemble into hollow spheres ranging in size from 100 to 5000 nanometers in diameter, consisting of several layers of DNA, lipids and payload.
According to Professor Lo, the beauty of the project is that the drugs are enclosed in the very "body" of the delivery vehicle. Having the size of a virus, the DNXOME is captured by the cell membrane and enters the cell in the same way as it happens with a virus. DNXomes can be made addressable by binding ligand molecules of certain types of cells to them, for example, cancer cells.
DNXomes begin with short chains of synthetic DNA, certain sections of which are complementary to sections of another chain. This property allows DNA molecules to combine into microscopic Y-shapes. A lipid molecule is connected to the "tail" of such a Y-block of DNA, and a fluorescent dye can be attached to the "hands" to track the structure in the cell. Drugs or RNA are chemically bound to Y-blocks. A lot of Y-blocks are assembled into a sphere the size of a virus, capable of delivering its payload to cells and their nuclei. (Picture from the website news.cornell.edu )
How the release of therapeutic agents occurs inside the cell is still a "black box", Professor Lo comments on the work. However, this also applies to other drug delivery systems. However, tests show that the "package" reaches the addressee: scientists loaded DNXomes with fluorescent dye, introduced them into the culture of hamster ovarian cells, and micrographs showed that the cells glow under ultraviolet light. It should be noted that the cargo was delivered both to the cytoplasm of cells and to the nucleus – an important advantage when simultaneous delivery of several drugs is necessary, since different drugs may have different cellular targets. In subsequent experiments, scientists confirmed the ability of DNXOMES to deliver several drugs simultaneously, as well as miRNAs.
Professor Lo and his colleagues named their nanoparticles DNXOMES by analogy with liposomes (translated from Latin "soma" means "body").
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