Mesoporous
silica nanoparticles (MSNs), based on the MCM-41 matrix,
were functionalized with amino groups, and then with hyaluronic acid
(HA) or chitosan (CHIT) to fabricate bioactive conjugates. The role
of the functional groups toward cytotoxicity and cellular uptake was
investigated using 3T3 mouse fibroblast cells. A very high biocompatibility
of MSN-NH2, MSN-HA and MSN-CHIT matrices was assessed through
the MTS biological assay and Coulter counter evaluation. No significant
differences in cytotoxicity data arise from the presence of different
functional groups in the investigated MSNs. Fluorescence microscopy
experiments performed using fluorescein isothiocyanate-conjugated
MSN-NH2, MSN-HA, and MSN-CHIT, and transmission electron
microscopy experiments performed on slices of the investigated systems
embedded in epoxy resins give evidence of significant differences
due to type of functionalization in terms of cellular uptake and stability
of the particles in the biological medium. MSN-NH2 and
MSN-HA conjugates are easily internalized, the uptake of the HA-functionalized
MSNs being much higher than that of the -NH2-functionalized
MSNs. Differently, MSN-CHIT conjugates tend to give large aggregates
dispersed in the medium or localized at the external surface of the
cell membranes. Both fluorescence microscopy and TEM images show that
the MSNs are distributed in the cytoplasm of the cells in the case
of MSN-NH2 and MSN-HA, whereas only a few particles are
internalized in the case of MSN-CHIT. Flow cytometry experiments confirmed
quantitatively the selectively high cellular uptake of MSN-HA particles.
Biomedical application of nanoparticles is largely associated to their fate in biological media which, in turn, is related to their surface properties. Surface functionalization plays a key role in determining biodegradation, cytotoxicity and biodistribution through interactions which may be mediated by the macromolecules occurring in biological media. A typical example is given by several proteins which lead to the formation of coated nanoparticles referred as protein corona. In this work we focus on mesoporous silica nanoparticles which, due to their intrinsic textural features, show potential as carriers for sustained drug release. Mesoporous silica nanoparticles functionalized by different biopolymers such as hyaluronic acid and chitosan were synthesized and characterized through small angle X-rays scattering, thermal analysis, and infrared spectroscopy. Biopolymer-coated mesoporous silica nanoparticles were used to investigate the interaction with bovine serum albumin, and to point out the role of different biopolymer coating. Gold-conjugated-bovine serum albumin was used to gain evidence on the occurrence of surface bound proteins enabling direct observation by transmission electron microscopy. Our findings provide insights on how different biopolymers affect the formation of a protein corona around functionalized mesoporous silica nanoparticles.
Mesoporous silica nanoparticles (MSNs) were functionalized with amino groups (MSN-NH) 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 (8-15 kDa), HA (30-50 kDa) and HA (90-130 kDa), were used. The MSN-HA, MSN-HA, and MSN-HA 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-HA, which was smaller than that of MSN-HA and MSN-HA 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-NH and MSN-HA than for MSN-HA and MSN-HA samples. Cellular uptake experiments carried out at 4 °C showed that the internalization process was inhibited for MSN-HA samples but not for MSN-NH. This suggests the occurrence of two different mechanisms of internalization. For MSN-NH the uptake is mainly driven by the attractive electrostatic interaction with membrane phospholipids, while MSN-HA internalization involves CD44 receptors overexpressed in HeLa cells.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.