Nanoparticles deliver drugs under immune system radar

Scientists have designed ’stealth nanoparticles’ that can deliver drug payloads without detection by the immune system, thereby preventing adverse reactions.

A team from Brighton and Copenhagen universities found that subtle differences in the architecture of nanoparticle surface coatings had a marked effect on immune system response — essentially allowing them to engineer a particle with ’stealth properties’.

Nanoparticles are increasingly being investigated in drug delivery as they can potentially carry their payload directly to diseased cells or tumours with a reduced dosage and therefore fewer side effects.

However, there are still some major obstacles to overcome before they become mainstream, as project collaborator Dr Christy Hunter from Brighton told The Engineer: ‘One of the key issues, if you look at all the nanomedicines that are used at the moment, is that they can cause anaphylactic-type reactions in patients.

‘If you don’t understand the immunology of the interactions, these medicines will never really come to true fruition — you have to have an absolute mechanistic understanding.’

The team started with polystyrene particles of a similar size to viruses at around 50–200nm. However, when injected into the blood these particles were intercepted by an enzyme cascade called the complement system (which is part of the larger immune system).

They then experimented with various concentrations and densities of copolymer poloxamine-908 coatings, which had an effect on the resulting surface conformation of the nanoparticles.

‘At lower concentrations, you get a surface covering in which you might have the polymers in a mushroom shape, or if you put more on there you start getting a brush shape. The conformation has a direct effect on how the [immune] system is switched on.’

Hunter explained the key was to designing a coating that was hydrophilic enough to be compatible with biological fluids and yet evade complement activation.

Prof Moein Moghimi from Copenhagen, who worked on the project, added: ’Our newest research indicates that we should be very cautious when designing the surface of the nanoparticles.’

Moghimi told The Engineer that his group is now looking at whether they can make the surface of carbon nanotubes compatible with the body’s defences through polymer modifications. Carbon nanotubes are receiving increasing attention in experimental medicine for cancer imaging and therapy.