Applications · Oncology

Carriers that switch on inside the tumour

Cancer is where nanoscale delivery was first expected to transform therapy, and where the gap between injected dose and dose reaching the tumour is most visible. Designing carriers for oncology means engineering for a hostile, heterogeneous and constantly adapting target.

6.2×: Intratumoural payload
-51%: Hepatic accumulation
pH 6.5: Charge-switch trigger

Overview

Why delivery decides outcomes in oncology

Most systemically administered nanoparticles never reach a solid tumour. Meta-analyses of preclinical studies put the median delivered fraction well below one percent of the injected dose; the rest is captured by the liver, spleen and mononuclear phagocyte system. Raising that fraction, and controlling what happens to the payload once it arrives, is the central engineering problem in cancer nanomedicine.

Nucleic-acid payloads widen what a carrier can do in a tumour. siRNA silences drivers that small molecules cannot drug, mRNA makes tumour or immune cells produce therapeutic proteins, and CRISPR components knock out resistance genes or engineer immune effector cells. Each payload has a different intracellular destination, and each needs a carrier that survives the circulation and releases its cargo only where it should.

Our oncology work focuses on carriers whose surface changes in response to the tumour itself. A near-neutral, PEG-shielded particle circulates quietly; in the mildly acidic extracellular space of a tumour (pH ~6.5–6.8) its ionisable groups protonate, the surface turns cationic and adhesive, and uptake by tumour cells rises while off-target binding in healthy tissue stays low.

Delivery barriers

What stands in the way

Clearance before arrival

Serum proteins form a corona within seconds, and Kupffer cells and splenic macrophages remove opsonised particles. Surface density of PEG, particle size and charge govern circulation half-life.

Leaky but heterogeneous vessels

The enhanced permeability and retention (EPR) effect is strong in fast-growing mouse xenografts but patchy in human tumours. Accumulation varies between patients, between lesions and within a single lesion.

Dense stroma and high pressure

Fibrotic stroma and elevated interstitial fluid pressure, extreme in pancreatic cancer, stop particles a few cell layers from the vessel wall. Smaller carriers and stroma-modulating co-therapies push penetration deeper.

Endosomal escape

Even inside a tumour cell, most cargo stays trapped in endosomes and is degraded. Ionisable lipids and polymers that buffer or destabilise endosomal membranes decide whether siRNA or mRNA ever reaches the cytoplasm.

Design principles for tumour-selective carriers

Selectivity in oncology comes from stacking several modest advantages. A carrier that circulates longer, leaves leaky vessels, binds more strongly in acidic tissue and releases its cargo only after endocytosis reaches a therapeutic window no single feature delivers alone.

pH-responsive chemistry is the backbone of our approach. Ionisable lipids and poly(beta-amino ester) segments with tuned pKa stay largely uncharged in blood, gain charge in the tumour interstitium and become strongly cationic in late endosomes, where they disrupt the membrane and release the payload.

Particle size of 50 to 100 nm balances extravasation against renal and hepatic capture.
Sheddable PEG-lipids give stealth in circulation, then leave the surface so the carrier can bind its target.
Active ligands (folate, RGD peptides, transferrin, antibody fragments) add receptor-mediated uptake on top of passive accumulation.
Biodegradable ester linkages limit carrier accumulation over repeated dosing cycles.

Gene delivery for cancer immunotherapy

The fastest-moving use of non-viral carriers in oncology is immune engineering. CAR-T and TCR-T cells are manufactured today mostly with viral vectors; mRNA electroporation and lipid or polymer nanoparticles offer transient, lower-cost alternatives, and in vivo CAR generation aims to skip ex vivo manufacturing entirely.

Personalised mRNA cancer vaccines encoding patient-specific neoantigens, delivered in lipid nanoparticles, have reported encouraging relapse-free survival in melanoma when combined with checkpoint inhibitors. The carrier's job there is lymph-node and dendritic-cell delivery, not tumour accumulation.

From mouse models to patients

Subcutaneous xenografts in mice tend to exaggerate passive tumour accumulation. Orthotopic and patient-derived models, with realistic stroma and vasculature, give a more honest estimate of how much payload will reach a human tumour.

Repeated dosing raises its own questions: antibodies against PEG can accelerate clearance of later doses, and cationic carriers can trigger complement activation. Our programmes test multi-dose pharmacokinetics early rather than after lead selection.

Payloads

What gets delivered, and what it needs

Payload	What it does in cancer	Delivery requirement
siRNA	Silences oncogenes, resistance genes or immune checkpoints	Cytoplasmic release; repeat dosing
mRNA	Expresses cytokines, tumour antigens or suicide genes	Cytoplasmic release; transient expression
Plasmid DNA	Long-lived expression of immune modulators	Nuclear entry; low innate sensing
CRISPR RNP	Knocks out resistance genes or edits immune cells	Protein-compatible carrier; fast release

How success is measured

Tissue distribution by fluorescence or radiolabel imaging, tumour-to-liver ratio
Target knockdown by qPCR and western blot in tumour tissue
Tumour growth inhibition and survival in orthotopic models
Immune infiltration by flow cytometry and immunohistochemistry
Liver enzymes, cytokines and complement activation for safety

Browse the Assay Library →

Programmes in this area

BB-101
Solid tumours — pH-responsive siRNA carrier
IND-enabling · Meridian Pharma
BB-114
Pancreatic adenocarcinoma — stromal-penetrating payload
Preclinical · Undisclosed

See the full pipeline →

Other application areas

02 / Immunology & vaccines →03 / Neurology →04 / Rare disease →05 / Agricultural biotech →06 / Environmental sensing →All applications

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