Nanomedicine Approach Could Offer New Way to Target HER2+ Breast Cancer

Novel research suggests that using a nano-molecularly imprinted polymer (nanoMIP) may offer a unique and effective way to treat HER2-positive breast cancer. The research at this point is restricted to the laboratory and in mice, but it shows promise at limiting tumor growth in those settings.

“Rapid development in nanotechnology towards the advance of nanomedicine products holds great promise to improve therapeutic strategies against cancer,” wrote study authors led by Zhen Liu, MD, PhD, of Nanjing University in China. Molecularly imprinted nanoparticles have been shown in other cancers to be capable of blocking pathways that are crucial for cell proliferation. “Compared with antibodies, MIPs have advantages such as easy preparation, chemically stable, and low cost.” They published the new research in Angewandte Chemie.

The new research involved nanoMIPs that can block the HER2 signaling pathway, inhibiting the growth of HER2-positive cancers. While available HER2-targeted agents work by binding one of its domains or subdomains, the nanoMIP approach targets HER2 by binding its glycans. Once bound, this blocks the dimerization of HER2 with other EGFR members; this in turn blocks downstream signaling pathways and thus inhibits the growth of HER2-positive breast cancer cells.

The imprinting process was done using a method known as boronate affinity controllable oriented surface imprinting. A polymerizable mixture is separated into nanospheres, in the presence of the molecule they are designed to recognize; the biomolecules then “imprint” a signature on the spheres, allowing them to recognize the appropriate molecules.

First, they tested the nanoMIPs in vitro. These experiments found that the nanoMIP did in fact target HER2-positive cells, and inhibited cell proliferation by approximately 30%. They confirmed this in a mouse xenograft tumor model. After 21 days, the weight and size of tumors isolated from mice treated with the nanoMIP therapy were almost half those of control groups that were not treated. The authors noted that previously published work in mouse models found a range of tumor growth inhibition with pertuzumab and lapatinib of 38% to 74%, putting the new therapy in a reasonable range.

They also wrote that the nanoMIP treatment resulted in very little change in weight of the mice during therapy, suggesting there is “almost no biological toxicity.”

They concluded that the in vitro and in vivo studies demonstrate a viable new strategy for treating HER2-positive breast cancer. “This study provided robust evidence for using nanoMIPs as a new option of nanomedicine for effective therapy of cancer,” they wrote. “Since many signaling proteins are glycoproteins and the imprinting protocol employed is applicable for various glycans, the strategy presented herein can be facilely extended to many other signaling pathways.”