Mesoporous Silica Nanoparticles Functionalized with Hyaluronic Acid and Chitosan Biopolymers. Effect of Functionalization on Cell Internalization

Abstract

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.

Silica‐modified Electrodes for Electrochemical Detection of Malachite Green

“…. The amino‐grafted sample (MCM‐41‐NH 2 ) was obtained through post‐synthesis functionalization using APTES (20 % w/w) as amino‐precursor in anhydrous toluene as described in ref . The textural characterization was carried out with an ASAP 2020 instrument, by determining the N 2 adsorption/desorption isotherm at 77 K. SBA‐15 and MCM‐41 samples were heated at 250 °C at a rate of 1 °C/min under vacuum for 12 h, while MCM‐41‐NH 2 was heated at 110 °C at the rate of 1 °C/min under vacuum for 24 h before analysis.…”

Pt(IV)/Re(I) Chitosan Conjugates as a Flexible Platform for the Transport of Therapeutic and/or Diagnostic Anticancer Agents

“…Chitosan proved not to be an efficient carrier for the studied metal drugs: it increases the AR of the free Pt complex but it does not reach high levels. Very recently, mesoporous SNP (MSNP) functionalized with amino groups and then with hyaluronic acid (HA) or chitosan (C), showed very significant differences in terms of cellular uptake: MSNP-NH 2 and MSNP-HA were distributed in the cytoplasm of 3T3 mouse fibroblast cells, whereas MSNP-C were not able to penetrate the cells [43]. This result is in line with the data obtained in the current study.…”

Interactions between bovine serum albumin and mesoporous silica nanoparticles functionalized with biopolymers

“…Moreover, the external surface of MSNs can easily be functionalized with target biomolecules, i.e. proteins/antibodies [27][28][29], peptides [30,31] or saccharides [32][33][34], that can be recognized by receptors overexpressed by tumor cells [35][36][37]. Alternatively, these macromolecules can modify their conformation, as a response to a change of environmental conditions (i.e.…”