RT Journal Article T1 Mesoporous Silica Nanoparticles Functionalized withHyaluronic Acid. Effect of the Biopolymer Chain Length onCell Internalization A1 Nairi, Valentina A1 Magnolia, Silvia A1 Piludu, Marco A1 Nieddu, Mariella A1 Caria, Cristian Antonio A1 Sogos, Valeria A1 Vallet Regí, María Dulce Nombre A1 Monduzzi, Maura A1 Salis, Andrea AB 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 HAS (8 -15 kDa), HAM (30-50 kDa) and HAL (90-130 kDa), were used. The MSN-HAS, MSN-HAM, and MSN-HAL materials were characterized through zeta potential and dynamic light scattering measurements at pH=7.4 and T=37°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-HAL, which was smaller than that of MSN-HAS and MSN-HAM samples. The cellular uptake of MSN-HA samples on HeLa cells at 37°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-HAS than for MSN-HAM and MSN-HAL samples. Cellular uptake experiments carried out at 4°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 receptorsoverexpressed in HeLa cells. PB Elsevier SN 0927-7765 YR 2018 FD 2018-02-12 LK https://hdl.handle.net/20.500.14352/11969 UL https://hdl.handle.net/20.500.14352/11969 LA eng NO RESEARCHER ID M-3378-2014 (María Vallet Regí)ORCID 0000-0002-6104-4889 (María Vallet Regí) NO Unión Europea. H2020 NO RAS and Fondazione di Sardegna NO MIUR NO Visiting Scientists 2016 program financed by the Regione Autonoma della Sardegna. DS Docta Complutense RD 4 abr 2025