Hyaluronan-coated nanoparticles for active tumor targeting: Influence of polysaccharide molecular weight on cell uptake

Here we aimed to correlate different molecular weights of hyaluronic acid (HA), 200, 800 and 1437 kDa, used to decorate poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs), to their cell uptakes. NP internalization kinetics in CD44-overexpressing breast carcinoma cells were quantified, using healthy fibroblast cells as reference. Actually, NP uptake and selectivity by tumor cells were maximized for NPs HA 800 kDa, while being minimum for NPs HA1400 kDa. This unexpected result could be explained considering that the interaction between NPs and tumor cells is dictated by rearrangement and conformation of that segment of HA chain that actually protrudes from the NPs. Overall, results obtained in this work point at how HA molecular weight, is pivotal project parameter in NP formulation to promote active targeting in the CD44 overexpressing cancer cells.

Automated summary

The study found that the molecular weight of hyaluronic acid plays a significant role in the uptake and selectivity of nanoparticles in CD44-overexpressing breast carcinoma cells. Specifically, HA 800 kDa nanoparticles exhibited the highest uptake response, while HA 1400 kDa nanoparticles showed the lowest uptake. The interaction between nanoparticles and tumor cells is influenced by the rearrangement and conformation of the HA chain segment protruding from the nanoparticles.