Biodegradable nanoparticles enable simultaneous delivery of two drugs to attack tumors

Researchers at Tel Aviv University have developed a new platform that uses polymer nanoparticles to deliver drug pairs to specific types of cancer, such as skin cancer and breast cancer. The researchers explain that having both drugs arrive at the tumor site together greatly amplifies the therapeutic efficacy and safety profile.

The study was published in the journal Science Advances.

Professor Ronit Sacchi Fainaro, senior author of the study, said: “Current cancer treatments often use a combination of drugs that work synergistically to enhance anti-cancer efficacy. However, these drugs differ in their chemical and physical properties, including their rate of degradation, circulation time in the bloodstream, and ability to penetrate and accumulate in tumors.

“Therefore, even if multiple drugs are administered simultaneously, they will not reach the tumor together and their combined effect will not be fully realized.To ensure maximum efficacy and minimal toxicity, , we sought a way to simultaneously and selectively deliver two drugs to the tumor site to repair the tumor site without damaging healthy organs. ”

Researchers have developed biodegradable polymer nanoparticles (which break down into water and carbon dioxide within a month) that can encapsulate two different drugs that enhance each other’s activity. These nanoparticles target cancer sites by binding to sulfate groups that bind to P-selectin, a protein that is expressed at high levels on cancer cells and new blood vessels formed by cancer cells and provides nutrients and oxygen. selectively induced.

The researchers loaded the platform with two sets of FDA-approved drugs. One is a BRAF inhibitor and a MEK inhibitor used to treat melanoma (skin cancer) that has a BRAF gene mutation (present in 50% of melanoma cases), and the other is a targeted PARP inhibitor and PD-L1 inhibitor. For breast cancer with BRCA gene mutations or defects. This new drug delivery system was tested in two settings: a 3D cancer cell model in the laboratory and an animal model representing both the primary tumor type (melanoma and breast cancer) and its brain metastases.

The findings showed that nanoparticles targeting P-selectin selectively accumulated in primary tumors and did not harm healthy tissue. Additionally, the nanoparticles successfully crossed the blood-brain barrier and precisely reached metastatic sites in the brain without damaging healthy brain tissue.

Furthermore, the combination of the two drugs delivered simultaneously was much more effective than administering the drugs separately, even at doses 30 times lower than in previous preclinical studies. Nanoparticle treatment significantly reduced tumor size, extended time to progression by 2.5 times over standard treatment, and extended the lifespan of mice treated with the nanoparticle platform. The mice had a median survival time that was two times higher compared to mice that received free drug and three times longer survival time compared to untreated controls.

Professor Thatch Fainaro said: “In our research, we developed an innovative platform using biodegradable polymer nanoparticles to deliver drug pairs to primary tumor and metastatic sites. “We found that the drug pair significantly enhanced treatment efficacy in BRAF-mutated skin.” Cancer, BRCA-mutant breast cancer and its brain metastasis.

“Our platform is versatile by design, allowing us to deliver many different drug pairs that enhance the effectiveness of each other, thereby allowing us to deliver many different drug pairs that enhance the effectiveness of each other, such as in glioblastomas (brain tumors), pancreatic ducts, etc. that express the P-selectin protein. It can improve the treatment of a variety of primary tumors and metastases, including adenocarcinoma and renal cell carcinoma. ”