Israeli and European researchers on Sunday unveiled a new approach to treating cancerous tumors by using biodegradable nanoparticles to simultaneously deliver two drugs to amplify their effects.

The findings offer hope for patients with
Breast, Skin, Pancreatic and Brain cancer.

The research team, led by Prof. Ronit Satchi-Fainaro and doctoral student Shani Koshrovski-Michael from the Department of Physiology and Pharmacology at Tel Aviv University’s School of Medicine, collaborated with an extensive network of experts across Israel, Italy, Portugal, and the Netherlands. The study’s findings were recently published in the peer-reviewed Science Advances journal.

Satchi-Fainaro explained the motivation behind the innovation: “Cancer treatment often involves a combination of drugs working synergistically to enhance their anti-cancer effects. However, differences in their chemical and physical properties—such as degradation rates and tumor penetration capabilities—often prevent them from reaching the tumor simultaneously, limiting their combined efficacy.”

To tackle this issue, the researchers developed polymeric nanoparticles capable of encapsulating two drugs and selectively targeting tumors. These nanoparticles biodegrade into water and carbon dioxide within a month, ensuring safety and reducing long-term side effects. By attaching sulfate groups that bind to P-selectin—a protein overexpressed on cancer cells and their blood vessels—the nanoparticles home in on the tumor, leaving healthy tissues untouched.

The team loaded the nanoparticles with two FDA-approved drug pairs. The first pair, BRAF and MEK inhibitors, targets melanoma with a BRAF gene mutation, found in 50% of melanoma cases. The second pair, PARP and PD-L1 inhibitors, addresses BRCA-mutated breast cancer. These mutations present well-defined molecular targets, making them ideal for testing precision drug delivery methods.

The platform was tested in 3D cancer cell models and animal models representing primary melanoma and breast cancer tumors.

The nanoparticles also successfully penetrated the blood-brain barrier, making it possible to treat brain metastases effectively without harming healthy brain tissue. The blood brain barrier is a highly selective and protective barrier of tightly-packed cells that separates the circulating blood from the brain and central nervous system. This protects the brain from harmful substances in the blood while allowing in essential nutrients. However, its selective nature poses challenges for delivering therapeutic drugs to the brain.

The dual-drug delivery method demonstrated superior effectiveness compared to separate drug administration, even at doses 30 times lower than those used in prior studies. Tumor size reduction and delayed progression were significant, with treated mice showing a 2.5-fold improvement in time to progression and a twofold increase in median survival compared to those receiving free drugs. Untreated control groups fared even worse, with survival rates three times lower than those of treated mice.

The technology is adaptable for a variety of drug pairs and cancer types, potentially extending its impact to other tumors that express P-selectin, such as pancreatic cancer and glioblastoma, a highly aggressive form of brain cancer.

“This technology can transport various drug pairs that enhance each other’s effects, improving treatment for a wide range of cancers expressing the P-selectin protein,” Satchi-Fainaro said.

***