Researchers believe they have found a way to make certain anticancer agents safer without compromising their efficacy.
The team noted that Aurora B kinase inhibitors and other agents targeting the cell cycle have proven effective but highly toxic in clinical trials.
In an attempt to solve this problem, the researchers turned to nanotechnology. They encapsulated the Aurora B kinase inhibitor AZD2811 in polymeric nanoparticles called Accurins.
Susan Ashton, of AstraZeneca in Macclesfield, Cheshire, UK, and her colleagues developed the Accurins and described the work in Science Translational Medicine. The work was funded by AstraZeneca.
The Accurins consist of block copolymers of poly-D,L-lactide and poly(ethylene glycol). The researchers used an ion pairing approach to efficiently encapsulate AZD2811 and control release of the drug.
They found the Accurins could release AZD2811 continuously for more than 1 week in vitro. The nanoparticles also reduced tumor phosphorylated histone H3 levels in vivo for up to 96 hours after a single administration.
The researchers tested the AZD2811 Accurins in mice with diffuse large B-cell lymphoma and rats with colorectal tumors. The nanoparticles accumulated specifically in tumors, where they slowly released AZD2811 to cancer cells.
Compared to AZD1152 (a water-soluble prodrug of AZD2811), the AZD2811 Accurins blocked tumor growth more effectively at one-half the drug dose and caused fewer side effects in the rodents.
Based on these results, the researchers said Accurins could provide efficacy and tolerability using a more convenient dosing regimen, which may extend the utility of Aurora B kinase inhibition to a broader range of hematologic and solid tumor malignancies.
A phase 1 study (NCT02579226) testing AZD2811 Accurins in advanced solid tumors is currently recruiting patients.
A related Focus article published in Science Translational Medicine offers more insights on how Accurin nanoparticles may help enhance the safety and antitumor activity of Aurora kinase inhibitors and other molecularly targeted drugs.
