Chitosan/Hyaluronic Acid Nanoparticles: Rational Design Revisited for RNA Delivery

• DOI: 10.1021/acs.molpharmaceut.7b00320
• Publication Date: 2017-06-09T11:56:05Z
• Authors: Enrique Lallana; Julio M. Rios de ...; Annalisa Tirella; Maria Pelliccia; Arianna Gennari; Ian J. Stratford; Sanyogitta Puri; Marianne Ashford; Nicola Tirelli
• Keywords: Avidity; Internalization

Chitosan/hyaluronic acid (HA) nanoparticles can be used to deliver an RNA/DNA cargo cells overexpressing HA receptors such as CD44. For these systems, unequivocal links have not been established yet between chitosan macromolecular (molecular weight; degree of deacetylation, i.e., charge density) and nanoparticle variables (complexation strength, stability; nucleic protection; internalization rate) on one hand, transfection efficiency the other hand. Here, we focused role avidity in CD44-expressing HCT-116 a cellular model; employed two differently sized payloads (a large luciferase-encoding mRNA much smaller anti-Luc siRNA), small library chitosans (variable molecular weight deactylation). The RNA for showed—as expected—an inverse relationship: higher avidity–higher polyplex stability–lower efficiency. appears lead opposite effects: stability but also Surprisingly, best transfecting particles were those with lowest propensity release, although this might misleading example, same parameters that increase boost chitosan's endosomolytic activity, strong enhancement transfection. performance nonviral vectors therefore difficult predict simply basis carrier- or payload-related variables, more holistic consideration journey nanoparticle, from cell uptake cytosolic bioavailability payload, is needed. It noteworthy study showed optimal under slightly acidic conditions (pH 6.4), which promising applications tumoral extracellular environment. worth pointing out first time successfully delivered chitosan/HA nanoparticles.