Hyaluronated mesoporous silica nanoparticles for active targeting: influence of conjugation method and hyaluronic acid molecular weight on the nanovector properties

Valentina Ricci; Daniele Zonari; Stefania Cannito; Alessandro Marengo; Maria Teresa Scupoli; Manuela Malatesta; Flavia Carton; Federico Boschi; Gloria Berlier; Silvia Arpicco

doi:10.1016/j.jcis.2018.01.072

Hyaluronated mesoporous silica nanoparticles for active targeting: influence of conjugation method and hyaluronic acid molecular weight on the nanovector properties

J Colloid Interface Sci. 2018 Apr 15:516:484-497. doi: 10.1016/j.jcis.2018.01.072. Epub 2018 Jan 31.

Authors

Affiliations

¹ Department of Chemistry and NIS Centre, University of Torino, Via P. Giuria 7, Torino, Italy.
² Department of Drug Science and Technology, University of Torino, Via P. Giuria 9, Torino, Italy.
³ Department of Clinical and Biological Sciences, University of Torino, Corso Raffaello 30, Torino, Italy.
⁴ Research Center LURM (University Laboratory of Medical Research), University of Verona, Piazzale L.A. Scuro 10, Verona, Italy.
⁵ Department of Neurosciences, Biomedicine and Movement Sciences, Anatomy and Histology Section, University of Verona, Strada le Grazie 8, Verona, Italy.
⁶ Department of Computer Science, University of Verona, Strada le Grazie 15, Verona, Italy.
⁷ Department of Chemistry and NIS Centre, University of Torino, Via P. Giuria 7, Torino, Italy. Electronic address: gloria.berlier@unito.it.
⁸ Department of Drug Science and Technology, University of Torino, Via P. Giuria 9, Torino, Italy. Electronic address: silvia.arpicco@unito.it.

PMID: 29408139
DOI: 10.1016/j.jcis.2018.01.072

Abstract

We have prepared and evaluated the physico-chemical and biological properties of four different hyaluronated mesoporous silica nanoparticles (MSNs) samples (MSN/HA). Hyaluronic acid (HA) with two different molecular weights (200 and 6.4 kDa) was used for the conjugation of aminopropyl-functionalized MSN (NH₂-MSN), following two different procedures. Namely, samples HA200A and HA6.4A were prepared by reacting activated HA with NH₂-MSN (method A), while samples HA200B and HA6.4B were obtained carrying out HA activation in the presence of the nanoparticles (method B). The four samples showed similar hydrophilicity, but clear differences in the HA loading, textural properties, surface charge and stability of the suspensions. More in detail, conjugation using low molecular weight HA with method A resulted in low HA loading, with consequent scarce effects on dispersity and stability in physiological media. The highest yield and corresponding best performances were obtained with method B using high molecular weight HA. HA loading and molecular weight also influenced in a concerted way the biological response towards the MSNs of CD44 target cancer cells (CD44⁺) and control cells (CD44^-): MDA-MB-231 and A2780, respectively. The absence of cytotoxicity was assessed. Moreover, the targeting ability of the best performing MSN/HA was confirmed by cellular uptake studies.

Keywords: Active targeting; CD44 receptor; Hyaluronic acid; Hydrophilicity; Infrared; MSN; Mesoporous silica nanoparticles; Water adsorption.