Researchers at Tel Aviv University have developed a new platform using polymer nanoparticles to deliver drug pairs to specific cancer types, including skin cancer and breast cancer. The researchers explain that having both drugs arrive at the tumor site together significantly amplifies their therapeutic effects and safety profiles.

The research was published in the journal Scientific advances.

Professor Ronit Satchi-Fainaro, lead author of the study, explains: “Currently, cancer treatment often involves a combination of several drugs that act synergistically to enhance their anticancer effect. However, these drugs differ in their chemical and physical properties, such as their rate of degradation, their circulation time in the blood, and their ability to penetrate and accumulate in the tumor.

“Therefore, even if several drugs are administered simultaneously, they do not arrive at the tumor together and their combined effects are not fully realized. To ensure maximum effectiveness and minimum toxicity, we sought a way to deliver two drugs simultaneously and selectively. the tumor site without harming healthy organs.

Researchers developed biodegradable polymer nanoparticles (which break down into water and carbon dioxide within a month) capable of encapsulating two different drugs that enhance each other’s activity. These nanoparticles are selectively guided to the cancer site by attaching them to sulfate groups that bind to P-selectin, a protein expressed at high levels on cancer cells as well as on new blood vessels formed by cancer cells to provide them with nutrients and oxygen.

The researchers loaded the platform with two pairs of FDA-approved drugs: BRAF and MEK inhibitors used to treat melanoma (skin cancer) carrying a mutation in the BRAF gene (present in 50% of cases of melanoma), and PARP and PD-L1 inhibitors intended to breast cancer with a BRCA gene mutation or deficiency. The new drug delivery system was tested in two environments: in 3D models of cancer cells in the laboratory and in animal models representing both primary tumor types (melanoma and breast cancer) and their brain metastases.

The results showed that the nanoparticles, targeted to P-selectin, selectively accumulated in primary tumors and did not harm healthy tissues. Additionally, the nanoparticles successfully penetrated the blood-brain barrier, reaching brain metastases precisely without harming healthy brain tissue.

Additionally, the combination of two drugs administered simultaneously was found to be much more effective than administering the drugs separately, even at doses 30 times lower than in previous preclinical studies. Nanoparticle processing has significantly reduced tumor size, extending the time to progression by 2.5 times compared to standard treatments, and extending the lifespan of mice treated with the nanoparticle platform. The mice had a median survival 2 times higher than those receiving the free drugs and a survival 3 times longer than the untreated control group.

Professor Satchi-Fainaro says: “In our study, we developed an innovative platform using biodegradable polymer nanoparticles to deliver drug pairs to primary tumors and metastases. We found that drug pairs delivered in this way significantly improved their therapeutic effect in BRAF-mutated skin cancers and BRCA-mutated breast cancers as well as their brain metastases.

“Because our platform is versatile by design, it can carry many different drug pairs that enhance the effects of each, improving the treatment of a variety of P-expressing primary tumors and metastases. selectin, such as glioblastoma (brain cancer), pancreatic duct. adenocarcinoma and renal cell carcinoma.