A nanomedicine stack built from the molecule outward
Every Brilliant Blue Biosciences programme starts with the barrier a therapy has to cross. The carrier, the targeting ligand and the analytical method are then engineered together rather than assembled from off-the-shelf parts.
Anatomy of an ionisable lipid nanocarrier
Five components, each with one job. Changing any of them changes where the particle goes and whether its payload survives the journey.
How a nanoparticle escapes the endosome
Scroll through the six stages between injection and protein production. Endosomal escape is the step where most non-viral delivery is lost.
- 01
Circulation: neutral and shielded
At blood pH (7.4) the ionisable lipids are largely uncharged, so the particle carries little surface charge. A PEG-lipid layer limits protein adsorption and aggregation while the carrier travels to its target tissue.
- 02
Binding and uptake
Adsorbed apolipoprotein E or a surface ligand engages receptors on the cell. The membrane folds around the particle and pinches off, taking it inside by endocytosis — the PEG layer has largely shed by this point.
- 03
Early endosome: protonation begins
Proton pumps acidify the endosome to around pH 6.5. Ionisable lipids with an apparent pKa near 6.2–6.6 start to pick up protons, and the particle surface turns positive.
- 04
Late endosome: membranes destabilise
At about pH 5.5 the cationic lipids pair with anionic lipids in the endosomal membrane. Cone-shaped ion pairs favour non-bilayer (inverted hexagonal) structures that disrupt the membrane.
- 05
Escape into the cytosol
The payload passes through the disrupted membrane into the cytosol. Only a small fraction of internalised cargo — often estimated at a few per cent — escapes before the endosome matures towards the lysosome, which is why escape efficiency is a central design target.
- 06
The payload goes to work
Ribosomes translate the released mRNA into protein; siRNA would instead load into RISC to silence its target. The lipid components are metabolised and cleared.
How charge-shifting carriers switch on in a tumour
A carrier that is positively charged all the time sticks to everything. One that only becomes positive in acidic tumour tissue can stay discreet in the blood and turn active where it is needed.
- 01
Stealth in the bloodstream
A charge-shifting carrier circulates with a negative or near-neutral surface. Its amines are masked by an acid-labile group (for example a 2,3-dimethylmaleic amide) and a PEG layer, which keeps protein adsorption and uptake by healthy cells low.
- 02
Leaving leaky tumour vessels
Tumour blood vessels are often irregular and permeable, which can let nanocarriers pass into the tissue. This enhanced permeability effect varies widely between tumours and patients, so we do not rely on it alone.
- 03
Charge reversal in acidic tissue
The tumour microenvironment is mildly acidic (pH 6.5–6.8). The masking groups hydrolyse, the amines are exposed and the surface flips to positive — the carrier is now ‘switched on’ only where it is needed.
- 04
Targeted binding
The positive surface binds the negatively charged tumour cell membrane, and targeting ligands engage over-expressed receptors. Multivalent binding holds the carrier on the cell long enough for uptake.
- 05
Internalisation and release
The carrier enters by receptor-mediated endocytosis, then uses the same pH-driven endosomal escape to release its payload inside the tumour cell.
Ionisable carriers tuned for endosomal escape
Most delivery failures happen after uptake: the payload is swallowed by the endosome and degraded before it reaches the cytosol. Our ionisable lipid series shifts protonation state precisely in that pH window, releasing cargo where it stays active.
- pKa tuned between 6.2 and 6.6 for tissue-specific release
- PEG shedding kinetics matched to circulation half-life targets
- Compatible with mRNA, siRNA, ASO, peptide and small-molecule payloads
- Cryo-TEM and SAXS characterisation on every development lot
- Particle size range
- 12–80 nm
- Polydispersity index
- < 0.09
- Encapsulation efficiency
- 96.4%
- Batch scale
- 5 mL → 50 L
- Storage stability
- 30 days @ 4 °C
- Endotoxin
- < 0.25 EU/mL
Diagnostics that keep pace with the therapy
Precision delivery is only measurable with precision detection, so we develop the assay alongside the carrier.
Femtomolar detection
Cadmium-free quantum dots paired with affibody capture layers resolve biomarker concentrations three orders of magnitude below standard ELISA.
Multiplexed readout
Twelve distinct emission channels on a single chip let a panel be read in one 9-minute run without cross-talk correction.
Field-ready optics
The reader runs on a 12 V supply and tolerates 15–40 °C ambient, so assays travel to the sample instead of the reverse.
Scale-up without reformulation
Microfluidic mixing lets a larger batch be made by the same physics as the bench batch — not a redesign under deadline.
- 1
Formulation
Design-of-experiments across 40+ lipid ratios, executed by liquid handlers with automated DLS feedback.
- 2
Continuous mixing
Staggered herringbone micromixers hold residence time within ±2%, keeping size distribution identical at every scale.
- 3
Purification
Tangential-flow filtration and buffer exchange with in-line conductivity and UV monitoring.
- 4
Release testing
Size, zeta potential, RNA integrity, potency and sterility — documented to ICH Q2(R2).
Let's engineer the next delivery breakthrough together
We co-develop nanocarrier and biosensing programmes with pharma, biotech and academic groups — from target selection through scale-up.