RNA-Based Drug Delivery System Targets Cancer Cells Using Lipid Nanoparticles, Provides New Approach in Treating Multiple Myeloma

Over the past decades, advancements in our understanding of cell biology have led to more successful cancer treatments. However, many types of cancer are still fatal despite the effort invested by scientists in clinical research. To improve the survival rate of cancer patients, experts focus on targeted delivery of anti-cancer drugs.

A New Nanoparticle-Based Drug Delivery System

A group of researchers from Tel Aviv University and the Rabin Medical Center developed a drug delivery system using lipid nanoparticles (LNPs) similar to those used in making the COVID-19 vaccine. They contain RNA molecules used in silencing the CKAP5, the gene that encodes the cytoskeleton-associated protein 5. This protein inhibition prevents the cancer cell from dividing and eventually kills it.

The study was led by Professor Dan Peer, a pioneer in developing RNA therapies and Head of the Nanomedicine Laboratory at the Shmunis School of Biomedicine and Cancer Research. Their research focused on destroying multiple myeloma blood cancer cells under laboratory conditions where they are grown in flasks.

The research team designed targeted LNPs with a novel ionizable lipid to address this challenge of delivering RNA payload to multiple myeloma cells. To prevent the healthy cells from getting damaged, the nanoparticles were coated with anti-CD38 antibodies, specifically guiding them to the tumor cells inside the bone marrow. Then a novel xenograft multiple myeloma (MM) mouse model was employed to demonstrate the homing of MM cells to the bone marrow.

The result of the study reveals that under laboratory conditions, the nanoparticles developed by the researchers effectively eradicate about 90% of the cancer cells. Next, the novel treatment was tested on cancer samples obtained from MM patients at the Rabin Medical Center. After a single injection, it was discovered that the RNA could penetrate 60% of the multiple myeloma cancer cells in the bone marrow.

Lastly, animal models were also used to test the ability of the nanoparticles to reach the bone marrow. After examining the effectiveness of the treatment, it was found that two-thirds of the cancer cells were eradicated, and the animal models showed improvement in all clinical indicators.

According to study co-author Dana Tarab-Ravski, RNA-based therapy offers an excellent advantage since it can be developed quickly. Changing the RNA molecule allows the scientists to silence a different gene each time, customizing the treatment according to the disease's progression and the individual patient's specific needs.

What is Multiple Myeloma?

Multiple myeloma is a cancer that forms in white blood cells known as plasma cells. This blood cancer usually occurs in older people.

In a healthy body, plasma cells help a person fight infection by producing antibodies that detect and attack pathogens. In multiple myeloma, however, cancerous plasma cells accumulate in the bone marrow and crowd out healthy white blood cells. Instead of producing helpful antibodies, the cancer cells make abnormal proteins that can cause health complications.

Most blood cancers happen in the blood streams or lymph nodes, where they spread to the rest of the body. On the other hand, multiple myeloma cells begin and form tumors inside the bone marrow, making them very hard to reach.