Nanoparticle-mediated targeting of MAPK signaling predisposes tumor to chemotherapy

Jun 28 2009

An interdisciplinary team of researchers at Brigham and Women's Hospital and the Harvard-Massachusetts Institute of Technology (MIT) Division of Health Sciences and Technology has demonstrated a better way to deliver cancer drugs directly to tumors.

The researchers used specially engineered nanoparticles that can inhibit a signaling pathway and deliver a higher concentration of medication to the specific area. The research team, led by Shiladitya Sengupta, Ph.D., MIT, published its work in the Proceedings of the National Academy of Sciences of the United States of America.

The investigators constructed the nanoparticles from a biodegradable, biocompatible, U.S. Food and Drug Administration-approved polymer that they chemically engineered to deliver a MAPK inhibitor. By inhibiting the MAPK signaling pathway, which is involved in a majority of human tumors, the nanoparticles hinder the multiplication of cancerous cells and predispose those cells to the cytotoxic effects of chemotherapeutic drugs. The team also modified the polymer to increase drug loading twentyfold compared with the unmodified nanoparticle.

The combination of nanoparticles and the cancer drug cisplatin proved successful in preventing the growth of cancerous skin and lung cells and also induced cell death. When researchers gave the same combination to mice with melanoma, it inhibited tumor growth and enhanced the efficacy of the cancer drug. The entire tumor regressed in 50 percent of mice compared with none in the group receiving cisplatin and the inhibitor without nanoparticles.

In previous work, the group had demonstrated that a combination of two drugs delivered with a nanoparticle could exert superior anticancer effects. However, most cancers converge into a few pathways for survival and uncontrolled division. "The nanoparticles target pathways involved in multiple cancer types and can be applied to a diverse set of cancers, including hard-to-treat cancers, such as breast, pancreatic, and liver cancer," noted Dr. Sengupta. "The potential to add homing beacons on the surface of the nanoparticles can increase the efficiency of selectively targeting specific tumors and can abolish off-target side effects."

This work is detailed in the paper "Nanoparticle-mediated targeting of MAPK signaling predisposes tumor to chemotherapy." An investigator from the National Chemical Laboratory in Pune, India, also participated in this study. An abstract of this paper is available at the journal's Web site. View abstract