Mesoporous silica nanoparticles functionalized with hyaluronic acid. Effect of the biopolymer chain length on cell internalization

Mesoporous silica nanoparticles (MSNs) were functionalized with amino groups (MSN-NH2 ) and then with hyaluronic acid, a biocompatible biopolymer which can be recognized by CD44 receptors in tumor cells, to obtain a targeting drug delivery system. To this purpose, three hyaluronic acid samples differing for the molecular weight, namely HA(S) (8-15 kDa), HA(M) (30-50 kDa) and HA(L) (90-130 kDa), were used. The MSN-HA(S), MSN-HA(M), and MSN-HA(L) materials were characterized through zeta potential and dynamic light scattering measurements at pH = 7.4 and T=37 degrees C to simulate physiological conditions. While zeta potential showed an increasing negative value with the increase of the HA chain length, an anomalous value of the hydrodynamic diameter was observed for MSN-HA(L), which was smaller than that of MSN-HA(S) and MSN-HA(M) samples. The cellular uptake of MSN-HA samples on HeLa cells at 37 degrees C was studied by optical and electron microscopy. HA chain length affected significantly the cellular uptake that occurred at a higher extent for MSN-NH2 and MSN-HA(S) than for MSN-HA(M) and MSN-HAL samples. Cellular uptake experiments carried out at 4 degrees C showed that the internalization process was inhibited for MSN-HA samples but not for MSN-NH2. This suggests the occurrence of two different mechanisms of internalization. For MSN-NH2 the uptake is mainly driven by the attractive electrostatic interaction with membrane phospholipids, while MSN-HA internalization involves CD44 receptors overexpressed in HeLa cells. (C) 2018 Elsevier B.V. All rights reserved.