Going for gold could improve antisense cancer drugs
antisense cancer drugs that involve using gold nanoparticles, which
when combined with DNA, outperform conventional antisense agents.
Antisense drugs, which prevent genes from producing harmful proteins such as those that cause cancer, have the promise to be more effective than conventional drugs, but the pace of development of these new drugs has been slow.
However, Northwestern University scientists demonstrated a major step forward in research by attaching a number of strands of antisense DNA to the surface of a gold nanoparticle.
They achieved this by targeting mRNA sequences that code for enhanced green fluorescent protein (EGFP) expressed in a mouse cell.
The antisense sequence of the DNA attached to the nanoparticles was complementary to the mRNA for EGFP expression.
When the nanoparticles were introduced to the cells the fluorescence dimmed - a result of the nanoparticles binding to the mRNA and shutting down the protein's expression, or fluorescence.
The DNA become more stable and could bind to the target messenger RNA (mRNA) more effectively than DNA that is not attached to a nanoparticle surface like most commercial agents.
Once inside cells, the DNA-modified nanoparticles take on the role of messenger RNA sponges, binding to their targets and preventing them from being converted into proteins.
"In the future, this exciting new class of antisense material could be used for the treatment of cancer and other diseases that have a genetic basis," said Chad Mirkin, director of Northwestern's Center for Cancer Nanotechnology Excellence, who led the study.
When compared to antisense DNA complexed with commercial agents such as Lipofectamine and Cytofectin, the antisense nanoparticles were more effective in gene knockdown (decreasing gene expression and protein production), were less susceptible to degradation resulting in longer lifetimes, exhibited lower toxicity and were more readily absorbed by cells, exhibiting a greater than 99 per cent uptake.
"When mutations in the body's genetic material cause too many copies of certain proteins, cancer and other diseases can result," said Mirkin,
"Whereas typical drugs target the proteins, it is possible through gene therapy to target the genetic material itself before it is ever made into copies of harmful proteins. One way to target the genetic material is to block the messenger RNA by using 'antisense DNA,' which prevents the message from ever becoming a protein."
The findings will be published May 19 in the journal >Science.
