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

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 (NH-MSN), following two different procedures. Namely, samples HA200A and HA6.4A were prepared by reacting activated HA with NH-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.

Effects of the Molecular Weight of Hyaluronic Acid in a Carbon Nanotube Drug Delivery Conjugate

“…The HA receptor CD44, a ubiquitous transmembrane cell surface protein, is expressed at low levels on the surface of several normal cells and overexpressed in many cancer cells (Sneath and Mangham, 1998). We have recently reported that the MDA-MB-231 (human breast adenocarcinoma) cells display high expression of CD44 and that the A2780 (human ovarian carcinoma) cells did not express a detectable amount of CD44 (Ricci et al, 2018). Thus, to evaluate the cellular uptake and the cytotoxic activity of the previously prepared CNT/HA-DMPE, MDA-MB-231 and A2780 cells were chosen as CD44 + and CD44 − cells, respectively.…”

Advances in mesoporous silica nanoparticles for targeted stimuli-responsive drug delivery: an update

“…In addition, its structure presents both amino and carboxylic groups in stoichiometric proportion; so, the linkage of HA towards MSNs could be an important parameter. Along this line, Arpicco and coworkers made a systematic study on both aspects [83], finding that higher molecular weight HA (200 kDa) covalently bound in one-pot onto MSNs provided better targeting capabilities due to a lower self-condensation reaction rate.…”

Imaging techniques in nanomedical research

“…The capability of polyamidoamine dendrimers, 38 or nanosized polyethylenimine complexes 39 to deliver antisense oligonucleotides as well as of polyethylenimine-hexametaphosphate NPs to carry nucleic-acid-based therapeutics 40 to tumour cells was evaluated by CFM. The same technique was also used to test the uptake efficacy of solid lipid NPs aimed at HIV prevention, 41 silica NPs for tumour targeting, 42 , 43 or avidin-conjugated calcium phosphate NPs 10 and AuNCs for harnessing imaging and hyperthermia therapy of cancer. 44 CFM gave information also on the functionalization efficacy in increasing quantum dots uptake by cancer cells.…”