Cancer Treatment Combines Phototherapy with Drug, Gene Therapy

A cancer treatment that combines light-based, drug and gene therapy has led to complete tumor remission when applied to non-resected tumors and to the absence of tumor recurrence when applied following tumor resection in a colon cancer mouse model.

The therapy was administered through an adhesive hydrogel patch attached to the tumor site either before or after surgery. Embedded in the patch were spherical gold nanoparticles which released small interfering RNAs (siRNAs) against a key oncogene driver. Rod-shaped gold nanoparticles, also embedded in the patch, heated up when NIR radiation was applied to the local area, causing the release of chemotherapy and thermally induced ablation of the tumor.

Researchers at MIT are developing an adhesive patch that can stick to a tumor site, either before or after surgery. The patch delivers a triple-combination of drug, gene, and photo (light-based) therapy via specially designed nanospheres and nanorods, shown here attacking a tumor cell. Courtesy of Ella Maru.

When researchers at Massachusetts Institute of Technology (MIT) tested the triple-therapy treatment on mice, the mice demonstrated 100 percent remission when the patch was applied after surgery. In 40 percent of cases where the patch was not applied after surgery, the cancer returned. In mice where the tumor was not removed, the administration of the combination light, gene, drug therapy alone destroyed the tumor.

Releasing a triple combination therapy locally, at the tumor site, may increase the efficacy of the treatment, according to Natalie Artzi, a research scientist at MIT and an assistant professor at Brigham and Women's Hospital.

Conventional cancer therapies involve the systemic delivery of anticancer agents that neither discriminate between cancer and normal cells nor eliminate the risk of cancer recurrence. In conventional treatments only a small portion of the drug reaches the tumor site itself.

"This means that we are treating both the source of the cancer -- the tumor -- and the metastases resulting from that source, in a suboptimal manner," said Artzi. "That is what prompted us to think a little bit differently, to look at how we can leverage advancements in materials science, and in particular nanotechnology, to treat the primary tumor in a local and sustained manner."

The triple-therapy device can treat not only the tumor but any cells left at the site after surgery, preventing the cancer from recurring or metastasizing. Researchers envision that a clinician could remove the tumor, then apply the patch to the inner surface of the colon. As the patch degrades, the therapies are gradually released. The patch can also be used to deliver neoadjuvant therapy prior to a resection. It can be applied in a minimally invasive manner.

"This administration modality would enable, at least in early-stage cancer patients, the avoidance of open field surgery and colon resection," Artzi said. "Local application of the triple therapy could thus improve patients' quality of life and therapeutic outcome."

In the next phase of their work, the researchers hope to move to experiments in larger models, in order to use colonoscopy equipment not only for cancer diagnosis but also to inject the patch to the site of a tumor.

The research was published in Nature Materials (doi: 10.1038/nmat4707).