Multiple myeloma is an incurable bone marrow cancer that causes over 100,000 deaths annually. Known for its rapid and deadly spread, it is one of the most challenging diseases scientists face today. As cancer cells move to different parts of the body, they mutate, surpassing potential treatments. Severe cases of multiple myeloma that are resistant to chemotherapy typically result in a survival period of only 3–6 months. Scientists urgently need innovative therapies to prevent the spread of this disease and provide patients with a chance to fight it.

Recently, a study titled “In vivo bone marrow microenvironment siRNA delivery using lipid-polymer nanoparticles for multiple myeloma therapy” was published in the international journal Proceedings of the National Academy of Sciences. Scientists from the University of Pennsylvania and other institutions have developed a new RNA nanoparticle therapy that may prevent the mobility and mutation of multiple myeloma. This novel therapy may shut down a function in blood vessels that attracts cancer cells, rendering the pathway for multiple myeloma cell dissemination nonfunctional.

By blocking the “chemical GPS” that induces cancer cell migration, the therapy developed by researchers can halt the spread of multiple myeloma, helping to eliminate this type of cancer. Endothelial cells lining the blood vessels produce a specific protein crucial for cancer cell survival called CyPA. CyPA primarily assists in folding and transporting other proteins and can also activate the host body’s T-cell response during illness. However, when multiple myeloma is present, endothelial cells overexpress CyPA and secrete it into the blood vessels, enabling its malignant function. Researchers discovered that CyPA acts as a chemical attractant, pulling multiple myeloma cells from the bone marrow into the bloodstream and rapidly spreading them to other skeletal sites in the body.

Mitchell, one of the researchers, states, “To block dissemination, we aimed to use RNA therapy to shut down the function of CyPA and target the cancer microenvironment rather than the cancer cells themselves.” However, delivering nucleic acids to the bone marrow faces significant challenges due to complex biological barriers. To enable the entry of RNA into the hard-to-reach bone marrow, researchers needed to redesign the traditional transport tools of lipid nanoparticles.

In their study, they designed a novel hybrid nanoparticle that delivers small interfering RNA (siRNA) into endothelial cells, blocking the production of CyPA. In in vitro experiments, this therapy prevented cancer cell dissemination. In testing on mouse models, the therapy, whether used alone or in combination with chemotherapy, reduced tumor size and prolonged survival, decreasing resistance to chemotherapy. This research may help improve current therapies for the treatment of multiple myeloma and other types of cancer that spread through blood vessels. Utilizing this new targeted nanoparticle platform, researchers hope to investigate other types of cancer and diseases where CyPA is overexpressed.

By creating a barrier during the process of cancer spreading through the body, researchers are currently overcoming a longstanding obstacle in the treatment of multiple myeloma in humans, potentially providing genuine hope for patients diagnosed with this disease. In future research, investigators plan to explore other functions of the cancer microenvironment to better overcome drug resistance, cancer initiation, and metastasis. Currently, researchers are identifying potential targets for this type of therapy through collaborative studies. Once RNA nanoparticle therapy is proven safe in large animal models, this proof-of-concept research may progress to clinical trials.

In conclusion, the findings of this study demonstrate that the newly developed nanoparticle platform by researchers may offer a broad technology to deliver nucleic acid therapies into various human malignancies, including multiple myeloma, that reside in the bone marrow, exerting the corresponding therapeutic efficacy.