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It's so much more friendly with two
NEWS
Relaxed DNA offers improved cancer treatment NANOTECHNOLOGY DNA origami may prove to be an effective targeted delivery vehicle for the popular anticancer drug doxorubicin, according to Swedish researchers. Doxorubicin been used since the 1960s to treat a wide range of cancers. However, like many anticancer drugs it has issues with side effects, including heart arrhythmias and severe nausea. One way to diminish these problems is to encase the drug in a targeted delivery system that directs it to where it is actually needed in the body, and a known way to do this is to use nanoparticles with proteins on the outside that seek out cancerous cells. Now, a team led by Bjorn Hogberg at Karolinska Institute in Stockholm, Sweden, have presented in ACS Nano [Zhao, Y-X., et al., ACS Nano (2012) doi: 10.1021/nn3022662] a DNA origami capable of encasing, as well as slowing the release of, doxorubicin The addition of doxorubicin causes the twist in the DNA in vitro. double helix to relax. Courtesy, Bjorn Hogberg. DNA origami is the folding of DNA into threedimensional shapes on the nanoscale. “DNA-origami nanostructures are easy to modify with proteins and explains Hogberg. The team successfully designed a other molecules in specific patterns. Because of this, structure that was able to hold doxorubicin inside. “We many researchers are interested in using these types show that DNA origami can be used as a drug delivery of structures to create smart drug delivery vehicles,” system for the cancer drug doxorubicin.”
The DNA double helix is intrinsically twisted. However, the DNA origami used for this work was specifically designed so that the twist relaxed – i.e., the helix became less twisted – when it contained a doxorubicin molecule. “We found that by altering the twist of these structures, their drug release rate can be tuned,” says Hogberg. “The structure is designed to have an inherent twist when it is folded. When there is no doxorubicin, the structures are frustrated and display lots of strain. However, after adding the drug the constituent DNA actually ‘prefers’ to have doxorubicin intercalated to release this strain. By designing the structures in this way, we create nanostructures that bind doxorubicin harder, and releasing it slower,” he explains. “Because of our slow release, the particles will have time to accumulate in tumours before large parts of the drug have been released.” Next, the team plan to add targeting proteins to the DNA origami to see how they affect the drug delivery in vitro. “Secondly, in order to further examine this we would have to do an animal study to estimate the feasibility of this system as a real drug,” says Hogberg.
Nina Notman
It’s so much more friendly with two POLYMERS A hydrogel that can stretch to over 20 times its original length has been created by US-based scientists. Hydrogels are cross-linked polymers in a solution of water, and they have applications ranging from flexible contact lenses, to scaffolds for tissue engineering, to drug delivery. However most hydrogels do not stretch well and are brittle, limiting their potential. Stretchy, less brittle hydrogels could be used to replace damaged cartilage in human joints, in artificial muscles and in protective coverings for wounds, claim the scientists in Nature [Sun, J-Y., et al., Nature (2012) doi: 10.1038/ nature11409]. “Conventional hydrogels are very weak and brittle — imagine a spoon breaking through jelly,” said JeongYun Sun, a postdoctoral fellow at Harvard University who worked on this project. “But because [these gels] are water-based and biocompatible, people would like to use them for some very challenging applications like artificial cartilage or spinal disks. For a gel to
work in those settings, it has to be able to stretch and expand under compression and tension without breaking.” One possibility is to use double network hydrogels that contain two interpenetrating, cross-linked polymer networks. Together two hydrogels can exhibit properties not seen in either of the hydrogel’s separately. The team’s hydrogel is a hybrid of polyacrylamide and alginate in an 8:1 ratio. This double network is far stretchier than two components separately. Alginate alone, for example, ruptures when it is stretched to around 1.2 times its original length, where as the double network is not brittle and can be stretched to over 20 times its original length. The alginate network is held together by weak breakable ionic bonds, with calcium ions – added to the water during the synthesis – captured within it. Whereas the polyacrylamide network is held together by strong covalent bonds. Together they form a complex network
of cross-linked chains that reinforce each other. The captured calcium ions play a key role in the stretchiness: when the gel is stretched some of the calcium ions are released. This allows the gel to expand slightly, while the polymer chains themselves remain unchanged. The calcium ions can reform ionic bonds with the aliginate when the hydrogel is returned to its original size, meaning the hydrogel can be shrunk and restretched multiple times. It was also shown that once a hole cut in the hydrogel it was still able to stretch to up to 17 times its original length. This is particularly unusual, as many hydrogels fracture as soon as a hole appears. This property is due to the polyacrylamide’s ability to spread the pulling force over a large area. “The unusually high stretchability and toughness of this gel, along with recovery, are exciting,” said Suo.
Nina Notman
NOVEMBER 2012 | VOLUME 15 | NUMBER 11
477
Relaxed DNA offers improved cancer treatment NANOTECHNOLOGY DNA origami may prove to be an effective targeted delivery vehicle for the popular anticancer drug doxorubicin, according to Swedish researchers. Doxorubicin been used since the 1960s to treat a wide range of cancers. However, like many anticancer drugs it has issues with side effects, including heart arrhythmias and severe nausea. One way to diminish these problems is to encase the drug in a targeted delivery system that directs it to where it is actually needed in the body, and a known way to do this is to use nanoparticles with proteins on the outside that seek out cancerous cells. Now, a team led by Bjorn Hogberg at Karolinska Institute in Stockholm, Sweden, have presented in ACS Nano [Zhao, Y-X., et al., ACS Nano (2012) doi: 10.1021/nn3022662] a DNA origami capable of encasing, as well as slowing the release of, doxorubicin The addition of doxorubicin causes the twist in the DNA in vitro. double helix to relax. Courtesy, Bjorn Hogberg. DNA origami is the folding of DNA into threedimensional shapes on the nanoscale. “DNA-origami nanostructures are easy to modify with proteins and explains Hogberg. The team successfully designed a other molecules in specific patterns. Because of this, structure that was able to hold doxorubicin inside. “We many researchers are interested in using these types show that DNA origami can be used as a drug delivery of structures to create smart drug delivery vehicles,” system for the cancer drug doxorubicin.”
The DNA double helix is intrinsically twisted. However, the DNA origami used for this work was specifically designed so that the twist relaxed – i.e., the helix became less twisted – when it contained a doxorubicin molecule. “We found that by altering the twist of these structures, their drug release rate can be tuned,” says Hogberg. “The structure is designed to have an inherent twist when it is folded. When there is no doxorubicin, the structures are frustrated and display lots of strain. However, after adding the drug the constituent DNA actually ‘prefers’ to have doxorubicin intercalated to release this strain. By designing the structures in this way, we create nanostructures that bind doxorubicin harder, and releasing it slower,” he explains. “Because of our slow release, the particles will have time to accumulate in tumours before large parts of the drug have been released.” Next, the team plan to add targeting proteins to the DNA origami to see how they affect the drug delivery in vitro. “Secondly, in order to further examine this we would have to do an animal study to estimate the feasibility of this system as a real drug,” says Hogberg.
Nina Notman
It’s so much more friendly with two POLYMERS A hydrogel that can stretch to over 20 times its original length has been created by US-based scientists. Hydrogels are cross-linked polymers in a solution of water, and they have applications ranging from flexible contact lenses, to scaffolds for tissue engineering, to drug delivery. However most hydrogels do not stretch well and are brittle, limiting their potential. Stretchy, less brittle hydrogels could be used to replace damaged cartilage in human joints, in artificial muscles and in protective coverings for wounds, claim the scientists in Nature [Sun, J-Y., et al., Nature (2012) doi: 10.1038/ nature11409]. “Conventional hydrogels are very weak and brittle — imagine a spoon breaking through jelly,” said JeongYun Sun, a postdoctoral fellow at Harvard University who worked on this project. “But because [these gels] are water-based and biocompatible, people would like to use them for some very challenging applications like artificial cartilage or spinal disks. For a gel to
work in those settings, it has to be able to stretch and expand under compression and tension without breaking.” One possibility is to use double network hydrogels that contain two interpenetrating, cross-linked polymer networks. Together two hydrogels can exhibit properties not seen in either of the hydrogel’s separately. The team’s hydrogel is a hybrid of polyacrylamide and alginate in an 8:1 ratio. This double network is far stretchier than two components separately. Alginate alone, for example, ruptures when it is stretched to around 1.2 times its original length, where as the double network is not brittle and can be stretched to over 20 times its original length. The alginate network is held together by weak breakable ionic bonds, with calcium ions – added to the water during the synthesis – captured within it. Whereas the polyacrylamide network is held together by strong covalent bonds. Together they form a complex network
of cross-linked chains that reinforce each other. The captured calcium ions play a key role in the stretchiness: when the gel is stretched some of the calcium ions are released. This allows the gel to expand slightly, while the polymer chains themselves remain unchanged. The calcium ions can reform ionic bonds with the aliginate when the hydrogel is returned to its original size, meaning the hydrogel can be shrunk and restretched multiple times. It was also shown that once a hole cut in the hydrogel it was still able to stretch to up to 17 times its original length. This is particularly unusual, as many hydrogels fracture as soon as a hole appears. This property is due to the polyacrylamide’s ability to spread the pulling force over a large area. “The unusually high stretchability and toughness of this gel, along with recovery, are exciting,” said Suo.
Nina Notman
NOVEMBER 2012 | VOLUME 15 | NUMBER 11
477