mRNA Vaccines Against Cancer Use Polymer-Based Nanoparticles for Targeted Drug Delivery

Scientists from Johns Hopkins Medicine developed a nanoparticle that could potentially improve the delivery of vaccines based on messenger ribonucleic acid (mRNA). These vaccines can fight infectious diseases such as COVID-19 and non-infectious diseases such as cancer.

Challenges in Making mRNA Vaccines

Developing mRNA COVID-19 vaccines based on nanoparticles are made from lipids and typically injected into the muscle. Although the muscle contains many cells that can express mRNA leading to an antibody response, few dendritic cells seek and destroy cancer cells. Scientists hope vaccines focusing on cancer treatment can be further improved by enhancing their potential to reach dendritic cells with mRNA instructions.

However, scientists find it difficult to inject lipid-based vaccines into the bloodstream because they tend to travel directly to the liver, where they get degraded. Customarily, the cell-targeting process is accomplished by using protein attachment to a nanoparticle that binds to the target cell's surface. Scientists express that such approaches lead to manufacturing challenges.

Breakthrough in Vaccine Designs

The Johns Hopkins University School of Medicine researchers responded to this challenge by developing a different approach to cancer treatment. Led by biomedical engineering professor Jordan Green, they aim to create a nanoparticle that will not be sent directly to the liver and can instruct immune system cells to find and destroy the intended target.

To make this possible, the mRNA contents of the nanoparticles are required to reach, enter, and be expressed in dendritic cells. After being expressed, the mRNA is degraded quickly, and as a result, the resulting immune cell response can last longer even after the mRNA and the nanoparticles have long gone.

Green and his team have tested various materials as they decided to encase a desired mRNA in a polymer-based storage. The research team engineered the water-loving and water-phobic nanoparticle molecules to their desired ratio. This will be the key to making the nanoparticle more suitable for encapsulating mRNA and making it easier to enter the target cell.

Disulfide bonds were used by Green and his colleagues in making nanoparticles that can degrade quickly once inside the target cell. The nanoparticles were also constructed using polymers containing end-capping molecules with an attraction for a specific tissue type. Finally, an adjuvant was added by the researchers to the nanoparticle, serving as a helper in activating the dendritic cell.

The decomposable, polymer-based nanoparticle carrying an mRNA-based vaccine was first tested in cells cultured in the laboratory. When injected into mice's bloodstream, it successfully traveled to the spleen and activated the immune cells that fight cancer. Almost 80% of cells in the spleen reached by the nanoparticles were the targeted dendritic cells.

The treated mice survived melanoma twice as long, while double the number of mice with colorectal cancer survived long-term. Analysis of the mice reveals that half of the specialized immune cells with the potential to destroy unhealthy cells from cancer infection have been activated to enable recognition of specific invading cancer cells.