Researchers have packaged a widely used cancer drug into nanoparticles, more than doubling its effectiveness at destroying tumors. The results were published in Nature Communications.
The drug paclitaxel has been used for decades to fight breast, ovarian, lung and other cancers. But its effectiveness has been limited by its small molecular size and insolubility in water - properties that allow the body to clear the drug too quickly, reducing its accumulation in tumors.
Many molecular packaging systems have been developed to deliver the drug while counteracting these effects, with a protein-bound version of the drug called Abraxane currently the leading therapy. By surrounding molecules of paclitaxel with self-assembling spheres composed of amino acids, the researchers doubled tumor exposure to the drug compared to Abraxane while simultaneously reducing its effects on healthy tissue. This kept mice with tumors alive significantly longer and, in some cases, completely eradicated the tumors.
The big difference between Abraxane and this approach is the types of molecular bonds that are formed. In Abraxane, the paclitaxel is physically surrounded by albumin, a common blood protein. In the new packaging system, multiple copies of the drug are chemically bonded to an amino acid polypeptide, forming a water-soluble nanoparticle with the drug hidden in its core.
These nanoparticles are highly soluble in blood and are the perfect size to penetrate and accumulate in tumors where they take advantage of a tumor's acidic environment.
To test their system, the researchers used two groups of mice. The first group had human breast cancer growing in their own mammary glands. While none of the mice treated with Abraxane survived past 85 days, most of the mice treated with the new packaging system survived past 100 days.
A second group of mice had human prostate tumors growing under their skin. Similarly, while they did not survive past 60 days when treated with Abraxane, every single mouse treated with the new packaging system survived past 70 days, with some experiencing a complete cure.
As the mortality rates suggest, the technology showed a higher concentration of paclitaxel in the tumors with more staying power than Abraxane, while simultaneously showing much lower levels throughout the rest of the mice's bodies.
In future work, the researchers will begin applying the packaging system to other cancer drugs with the goal of developing a "one size fits all" technology to improve the effectiveness of many other cancer drugs.
Based on material originally posted by Duke University.