The shape of nanoparticles that carry DNA through the body can be changed to increase their effectiveness in fighting cancer and other diseases, a team of researchers concluded in a paper published today.
A team of researchers from Johns Hopkins and Northwestern universities changed the shape of the nanoparticles through a gene therapy technique that carries DNA into cells without the use of virus. The team details its nanoparticle work in a study published online today in the journal Advanced Materials.
The team conducted animal tests, all using the same particle materials and the same DNA. The only difference was in the shape of the particles: rods, worms, and spheres that mimic the shapes and sizes of viral particles.
Shapes were formed by packaging the DNA with polymers, then exposing them to various dilutions of an organic solvent. DNA's aversion to the solvent, with the help of the team's designed polymer, caused the nanoparticles to take on a given shape, surrounded with a "shield" to protect it immune cells.
"The worm-shaped particles resulted in 1,600 times more gene expression in the liver cells than the other shapes. This means that producing nanoparticles in this particular shape could be the more efficient way to deliver gene therapy to these cells,” said Hai-Quan Mao, Ph.D., an associate professor of materials science and engineering in Johns Hopkins' Whiting School of Engineering, and the study’s co-corresponding author, in a statement.
"These nanoparticles could become a safer and more effective delivery vehicle for gene therapy, targeting genetic diseases, cancer, and other illnesses that can be treated with gene medicine," Dr. Mao added.
Dr. Mao’s nanoparticles consist of compressed healthy snippets of DNA within protective polymer coatings. The particles do not deliver the genetic material until after they have moved through the bloodstream and entered the target cells, where the polymer degrades and releases DNA. That material serves as a template through which the cells can produce functional proteins against disease.
Dr. Mao, who has spent a decade developing nonviral nanoparticles for gene therapy, and colleagues were able to reshape them into rods, worms, and spheres with help from researchers at Northwestern using computer models run on Quest, the university's high-performance computing system.
The models allowed the study’s other co-corresponding author, Erik Luijten, Ph.D., associate professor of materials science and engineering and of applied mathematics at Northwestern's McCormick School of Engineering and Applied Science team to perform molecular dynamic simulations that mimic traditional lab experiments at a far faster pace. The computations were complex enough for some of them to require 96 computer processors working simultaneously for one month.
[Read the study abstract at http://onlinelibrary.wiley.com/doi/10.1002/adma.201202932/abstract].