N4 Pharma has been developing Nuvec® – a unique non-viral adjuvant delivery system for vaccines and cancer treatments. This silica nanoparticle has the potential to help commercialise cancer immunotherapy drugs and improve the effectiveness of viral vaccines.
Nuvec® silica nanoparticles have a unique irregular (spiky) surface structure, coupled with polyethyleneimine (PEI), that simply and effectively traps and protects nucleic acid (such as mRNA / pDNA) as it travels to the cells. Our pre-clinical research work is seeking to demonstrate/confirm that:
- The Nuvec® particle carrying the DNA/RNA attaches to the cell membrane and is taken up into the cell via general and dynamin endocytosis.
- Once inside, PEI changes its charge and begins to disassociate from the particle, releasing some DNA/RNA.
- The particle spikes then start to disintegrate, releasing more of the nucleic acid into the endosome.
- The released PEI ruptures the endosome membrane releasing the DNA/RNA into the cytoplasm.
- The DNA is then free to be taken up into the nucleus where it expresses protein, which is presented on the cell membrane to attract and activate T-cells.
- The adjuvant nature of Nuvec® supports and increases T-cell activation for a strong attack of the cancer cells.
The diagram below shows the end-to-end mode of action for Nuvec® as it delivers DNA/RNA to antigen presenting cells.
The Nuvec® system is currently in the pre-clinical research phase. Some of its key features are outlined below:
- Adjuvant effect: Nuvec® is a natural adjuvant so it attracts a large number of innate immune cells which, in turn, leads to increased activation of the adaptive immune system (T and B cells), thus increasing the level of immune response against the target cancer cells.
- Favourable Th1 response: Nuvec® generates predominantly a Th1 response, characterized by a strong interferon gamma production. This response in necessary to fight intracellular parasites such as viruses or efficiently kill cancer cells.
- High loading capacity: The unique Nuvec® particle topography allows higher loading capacity, compared to alternative particle shapes. This property of the Nuvec® particle has been confirmed for both mRNA/pDNA.
- Strong binding: Novel design of nanoparticles to maintain strong binding to the particle
- Strong cellular uptake: Membrane and entry into the cell nucleus without leakage to liver
- Good biocompatibility/low toxicity: Proven low toxicity of the silica vesicles observed up to high doses in pre-clinical studies with low induction of systemic inflammatory cytokines. Well tolerated even up to high doses even in pre-clinical models.
- Predictable biodistribution and biodegradation: Following Si levels (determined by ICP-MS analysis) over time post single IV injection in animal model confirmed no significant change in Si detected in plasma, liver, lung, spleen and brain versus controls. Tracking the levels of intact Nuvec® particles showed that it did not disperse from the site of injection and was broken down in the body.
A series of studies supports the safety, efficacy and mode of action of Nuvec®. Download our whitepaper to read more.
If you would like any further information, please contact us.