Layer-by-layer assembly can provide a unique platform for the delivery of single drugs and synergistic drug combinations, and its use with drug-loaded core particles enables the co-encapsulation of DNA-damaging drugs, proteins and cytokines or other cytotoxic therapeutics with siRNA or other inhibitory drugs.   The use of a simple, alternating electrostatic assembly method to coat nanoparticles with polyelectrolyte assemblies can also lead to unique and dynamic outer surface layers that provide long blood half-lives, and exhibit an isoelectric point at physiologically relevant pH conditions to modulate nanoparticle uptake in hypoxic or inflamed tissues.   Furthermore, simple assembled bilayers exhibit different modes of cellular trafficking based on the chemical composition and molecular structure of the final adsorbed layer.  We have found that certain negatively charged polysaccharides and synthetic polypeptides can direct particles toward rapid intracellular uptake, slow caveolar uptake or extended membrane bound status without endosomal uptake in their engagement with ovarian cancer cells.   Furthermore, we can use these interactions to derive new strategies for targeted delivery of different therapeutics, ranging from cytotoxic  or silencing treatments to immuno-oncological approaches.<br/>

Engineering cellular interactions with nanolayered particles for controlled trafficking and delivery

256th National Meeting (2018)

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