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April 22, 2011

'DNAsomes' can deliver multiple drugs or genetic therapy

DNAsomes begin with short chains of synthetic DNA designed to be complementary over part of their length so they will join into microscopic Y-shapes. A lipid molecule is attached, and fluorescent dyes can be attached for tracking. Drugs or RNA are chemically bonded to the Y-shaped unit, then many units assembled into a sphere, about the size of a virus, that can enter cells and deliver their payload.

Cornell researchers are using synthetic DNA to make nanoparticles, dubbed DNAsomes, that can deliver drugs and genetic therapy to the insides of cells. DNAsomes, Luo said, can carry multiple drugs as well as RNA molecules designed to block the expression of genes, an improvement over other drug-delivery systems such as liposomes (tiny wrappers of the phospholipid molecules that make up cell membranes) or polymer nanoparticles. Also, some other delivery systems can be toxic to cells, the researchers said.

Journal Small - DNAsomes: Multifunctional DNA-Based Nanocarriers



Multifunctional DNAsomes: DNA–lipid amphiphiles self-assemble into novel “DNAsomes”—liposome-like core–shell structures with subunits composed of branched DNA–lipid hybrid molecules. These DNAsomes can be precisely tuned over a wide range in terms of both size and surface charge. More importantly, DNAsome is a natural carrier of small interfering RNA (siRNA) due to DNA–RNA base-pairing, enabling efficient co-delivery of drugs and siRNA. The DNAsome represents a universal multifunctional drug vector for simultaneous delivery of drugs, tracer dyes, or antibodies, along with genes, siRNA, or antisense nucleic acids.

In its natural habitat in the nucleus of a cell, DNA consists of long chain molecules that are complementary, attaching to one another like a string of Lego blocks over their entire length to form the famous double helix. The Luo research group creates short chains of synthetic DNA designed to attach over only part of their length so they will join into shapes like crosses, Ts or Ys.

DNAsomes are assembled from Y-shaped units, each made up of three strands of DNA. A lipid molecule is attached to the tail of the Y, and drugs to be delivered are chemically bonded to the arms. When the goal is to block the expression of genes with molecules of siRNA (small interfering RNA), the synthetic DNA can be designed with a section complementary to the RNA so that the RNA will loosely attach to it. Delivering siRNA has been a particular challenge for other drug-delivery systems, the researchers noted.

In water solution, the combination of DNA, which is attracted to water molecules, and lipids, which are repelled by water, causes the Y units to self-assemble into hollow spheres from 100 to 5,000 nanometers in diameter, consisting of multiple layers of DNA, lipid and cargo.

"The beauty of this is that the body of the thing is also a body of drugs," Luo said. About the size of a virus, the DNAsome will be engulfed by the cell membrane and taken into a cell in a similar way as a virus, he explained. The DNAsome can be tagged with molecules that target a particular kind of cell, such as a cancer cell.

What happens inside the cell to release the drugs is still a "black box," Luo said, as it is with other drug-delivery systems, but tests show that the cargo is delivered. The researchers loaded DNAsomes with a fluorescent dye and introduced them into a culture of hamster ovarian cells. Microphotos showed the ovarian cells glowing under ultraviolet light. Notably, the researchers found, the cargo had been delivered both to the cytoplasm and nucleus of the cells, an important consideration for multiple drug delivery, since different drugs might have different targets in the cell. In later experiments the researchers verified the ability of DNAsomes to deliver multiple drugs as well as siRNA.

DNAsomes are named by analogy with liposomes. The suffix --some comes from a Latin word meaning "body."

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