Scientists further understanding of delivering drugs through nanocarriers
SYRACUSE, N.Y.-- The ovarian cancer drug doxorubicin can be toxic to the heart.Giving a woman enough of the drug to be effective against her cancer maybe too much to be safe for her heart.
Scientists at Upstate Medical University are pairing doxorubicin withregular vitamin B2 in a new nanoformulation (that is, using microscopicparticles) to treat ovarian cancer-with encouraging results that aregentle on the heart.
“We were able to demonstrate significantly inhibited tumor growth and prolonged survival,” Juntao Luo, PhD, says in describing his research in the journal Biomaterials. Luo is an assistant professor of pharmacology whose research focuses on the use of nanocarriers for drug delivery.
A key piece of the success of the doxorubicin-vitamin B2 project isthe creation of what is known in scientific terms as a “well-definedlinear-dendritic telodendrimer nanoplatform.”
It’s known colloquially as a truck--a teeny-tiny truck made of a polymer.
Used separately, such high concentrations of doxorubicin are requiredin order to achieve the antitumor effects, which exposes the heart totoxic levels of the drug molecules. Doctors often warn patients not totake vitamin B2 if they are taking doxorubicin because the vitamin canweaken the drug.
When doxorubicin and vitamin B2 are paired on the drug-carryingtruck, however, they have what scientists call “synergy,” working morefavorably to kill cancer cells than either could alone.
The presence of vitamin B2 helps keep the doxorubicin molecules boundtogether on the polymer truck, minimizing the impact on the heart as ittravels the bloodstream en route to the tumor.
Another form of doxorubicin used to treat ovarian cancer is Doxil, amedication that is incorporated into another style of truck, made oflipids. Doxil reduces heart toxicity, but its truck structure is toolarge to effectively penetrate the tumor, Luo describes.
The blood vessel leading to the tumor has an opening that iscomparatively wide. Luo’s truck is small enough to travel deep into thetumor, delivering the drug where it can be most effective. This allowsmore cancer cells to be killed than by Doxil or by plain doxorubicinwithout Luo’s polymer truck.
After its work is done, the truck exits the body undetected through the urine.
“The nanoparticle reaches the tumor site easier and releases thedrug, with minimal effects on the heart,” Luo describes. “Our formationinhibits tumor growth much more efficiently.”
This summer, Luo is working with gynecologic oncologist Rinki Agarwal, MD,to establish protocols for collecting samples of ovarian tumors fromCentral New York women. The samples would provide the next step towardtesting this new treatment strategy. The scientists believe that testingthis novel formulation directly on patient-derived samples will bringthem a lot closer to bringing it to clinical trials.
Caption: Juntao Luo, PhD, is conducting research with a focus on the use of nanocarriers for drug delivery.