Nanoparticles are available as many different classes, made from both organic and inorganic materials. Organic nanoparticles have been translationally successful, including liposomes, lipids, and emulsions. Inorganic nanostructures made from materials like gold or silica have been emerging, but these have not progressed to the clinic as far as their organic counterparts.
What makes nanoparticles particularly attractive as delivery mechanisms is their multifunctionality. A variety of drugs, targeting moieties, imaging payloads can be attached to the structure. While these features are appealing to engineers and drug designers, from a translational perspective the more complex the nanoparticle is, the more difficult it will be to produce in large batches. As a result, most of the nanoparticle formulations in the clinic are simpler.
The mechanism by which nanoparticles are believed to extravasate from the blood to the tumour is the enhanced permeability and retention effect (EPR). Here, the vasculature of the tumour is less developed than healthy organs and therefore leaks nanoparticles from the bloodstream to the tumour.
EPR is a heterogeneous effect, meaning some tumours are leakier than others, and some individuals have leakier tumours than others. Therefore, companion diagnostics using imaging nanoparticles can identify patients more likely to benefit from nanoparticle therapies, modestly increasing clinical trial success rates.
There is also ongoing research into whether EPR is indeed the leading cause of the transfer of nanoparticles into the tumour site, with trans endothelial pathways being another route of extravasation.
Many small companies develop nanoparticle therapies but face funding and clinical trial hurdles, leading to partnerships or acquisitions by larger pharmaceutical firms. Targeted nanoparticles have shown promise but also clinical trial failures.
Effective nanoparticle therapies require application-driven design, relevant animal models, companion diagnostics, and well-characterized formulations to facilitate clinical translation and regulatory discussions.
