Key points:
- Researchers have developed a nanoparticle that can improve the delivery of mRNA vaccines for both infectious and non-infectious diseases.
- The team tested various materials and ultimately decided to encase a desired mRNA in a polymer-based vessel.
- After injection, mice with melanoma survived twice as long, and twice the number of mice with colorectal cancer survived long-term.
Johns Hopkins Medicine scientists have developed a nanoparticle they say has the potential to improve the delivery of mRNA-based vaccines for infectious diseases, like COVID-19, as well as non-infectious diseases, including cancer.
Jordan Green, professor of biomedical engineering, and his team tested various materials and ultimately decided to encase a desired mRNA in a polymer-based vessel. They engineered the nanoparticle’s ratio of water-loving to water-phobic molecules just right—a key to making the nanoparticle more apt to encapsulate mRNA, and making it easier to enter the target cell.
Then, the team used disulfide bonds to make the nanoparticles degrade quickly inside the target cell. The polymers used to construct the nanoparticles contained end-capping molecules that have an affinity for a specific tissue type. Finally, the researchers added an adjuvant to the nanoparticle to help activate the dendritic cell.
According to the study results in mice, the nanoparticle configuration was taken up by primary dendritic cells at levels about 50-fold higher than mRNA by itself. Nearly 80% of cells in the spleen that the nanoparticles reached were the target dendritic cells.
Additional experiments showed that half of mice with colorectal cancer survived long-term after receiving two injections of the new nanoparticle formulation plus an immunotherapy drug, compared with 10% to 30% that survived after treatment with other nanoparticle formulations and an immunotherapy drug or the immunotherapy drug alone.
Of the long-term surviving mice with colorectal cancer, all of them lived without additional treatment when the researchers gave them additional colorectal cancer cells, suggesting a long-term immunological response that prevented the cancer from returning.
The researchers also found that 21 days after treatment with the new nanoparticle, 60% of the cell-killing T-cells in the mice were armed to recognize and attack the colorectal cells. Similarly, in mice with melanoma, about half of the same type of T-cells were primed to attack melanoma.
“The nanoparticle delivery system was able to create an army of T-cells that can recognize cancer-linked antigen,” said Green. “This new nanoparticle delivery system may improve the way vaccines are given for infectious disease, and it may open a new avenue for treating cancer as well.”