Novel hydrogel gradually delivers RNA nanovaccines to shrivel tumors
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- Source: American Chemical Society
- Date: 18 Feb,2021
Messenger RNA (mRNA) vaccines to stop COVID-19 have made headlines around the world recently, but scientists also have been working on mRNA vaccines to treat or prevent other diseases, including some forms of cancer.
Cancer immunotherapy vaccines operate similarly to mRNA vaccines for COVID-19, except they trigger the immune system to attack tumors rather than a virus. These vaccines contain mRNA that encodes proteins made specifically by tumor cells. After the mRNA enters antigen-presenting cells, they begin making the tumor protein and displaying it on their surfaces, triggering other immune cells to seek and destroy tumors that also make this protein. However, mRNA is an unstable molecule that is quickly degraded by enzymes in the human body.
For cancer immunotherapy, researchers have tried using nanoparticles to safeguard and deliver mRNA, but they’re typically cleared from the body within 1-2 days following injection. Guangjun Nie, Hai Wang and colleagues wanted to come up with a hydrogel that, when injected beneath the skin, would slowly release mRNA nanoparticles, together with an adjuvant — a molecule that will help activate the immune system.
To develop their system, the investigators used ovalbumin (a protein found in chicken egg whites) as a model antigen. The group combined ovalbumin mRNA and an adjuvant with other chemicals to form a hydrogel. When injected under the skin of mice with melanoma tumors engineered to express ovalbumin, the hydrogel gradually released mRNA and adjuvant nanoparticles within a 30-day period.
The mRNA vaccine activated T cells and stimulated antibody production, causing tumors to shrink in the treated mice. In addition, in contrast to untreated mice, the vaccinated mice didn’t show any metastasis to the lung. These results demonstrate that the hydrogel has excellent potential for attaining long-lasting and effective cancer immunotherapy with only a single treatment, the researchers state.
Yin, Y., et al. (2021) In Situ Transforming RNA Nanovaccines from Polyethylenimine Functionalized Graphene Oxide Hydrogel for Durable Cancer Immunotherapy. Nano Letters. doi.org/10.1021/acs.nanolett.0c05039.