Researchers from the joint biomedical engineering program at North Carolina State University and the University of North Carolina at Chapel Hill report the development of daisy-shaped, nanoscale structures that are made predominantly of anticancer drugs. The scientists say their novel delivery system is capable of introducing a cocktail of multiple drugs into cancer cells.
"We found that this technique was much better than conventional drug delivery techniques at inhibiting the growth of lung cancer tumors in mice," explained Zhen Gu, Ph.D., an assistant professor in the joint biomedical engineering program. "And based on in vitro tests in nine different cell lines, the technique is also promising for use against leukemia, breast, prostate, liver, ovarian, and brain cancers."
To make the nanodaisies, the researchers begin with a solution that contains polyethylene glycol (PEG), which forms long strands that have much shorter strands branching off to either side. Researchers directly link the anticancer drug camptothecin (CPT) onto the shorter strands and introduce the anticancer drug doxorubicin (Dox) into the solution.
PEG is hydrophilic while CPT and Dox are hydrophobic. As a result, the CPT and Dox cluster together in the solution, wrapping the PEG around themselves. This results in a daisy-shaped drug cocktail, only 50 nanometers in diameter, which can be injected into a cancer patient.
Once injected, the nanodaisies float through the bloodstream until they are absorbed by cancer cells. In fact, one of the reasons the researchers chose to use PEG is because it has chemical properties that prolong the life of the drugs in the bloodstream. The scientists published their study (“Folding graft copolymer with pendant drug segments for co-delivery of anticancer drugs”) in Biomaterials.
Once in a cancer cell, the drugs are released. "Both drugs attack the cell's nucleus, but via different mechanisms," says Wanyi Tai, Ph.D., a former postdoctoral researcher in Dr. Gu's lab.
“Equipped with a PEG shell, the nanocarriers displayed good stability and can be internalized by a variety of cancer cell lines via the lipid raft and clathrin-mediated endocytotic pathway without premature leakage, which showed a high synergetic activity of CPT and Dox toward various cancer cells,” wrote the investigators. “In vivo study validated that the nanocarriers exhibited strong accumulation in tumor sites and showed a prominent anticancer activity against the lung cancer xenograft mice model compared with free drugs."
"Combined, the drugs are more effective than either drug is by itself," noted Dr. Gu. "We are very optimistic about this technique and are hoping to begin preclinical testing in the near future."