CD44-Targeted Carriers: The Role of Molecular Weight of Hyaluronic Acid in the Uptake of Hyaluronic Acid-Based Nanoparticles

Abstract

Nanotechnology offers advanced biomedical tools for diagnosis and drug delivery, stressing the value of investigating the mechanisms by which nanocarriers interact with the biological environment. Herein, the cellular response to CD44-targeted nanoparticles (NPs) was investigated. CD44, the main hyaluronic acid (HA) receptor, is widely exploited as a target for therapeutic purposes. HA NPs were produced by microfluidic platform starting from HA with different molecular weights (Mw, 280, 540, 820 kDa) by polyelectrolyte complexation with chitosan (CS). Thanks to microfluidic technology, HA/CS NPs with the same physical features were produced, and only the effects of HA Mw on CD44-overexpressing cells (human mesenchymal stem cells, hMSCs) were studied. This work provides evidence of the HA/CS NPs biocompatibility regardless the HA Mw and reveals the effect of low Mw HA in improving the cell proliferation. Special attention was paid to the endocytic mechanisms used by HA/CS NPs to enter hMSCs. The results show the notable role of CD44 and the pronounced effect of HA Mw in the NPs’ internalization. HA/CS NPs uptake occurs via different endocytic pathways simultaneously, and most notably, NPs with 280 kDa HA were internalized by clathrin-mediated endocytosis. Instead, NPs with 820 kDa HA revealed a greater contribution of caveolae and cytoskeleton components.

Synthesis of hyaluronic acid core–shell nanoparticles via simple microfluidic-assisted nanoprecipitation method for active tumor targeting

“…Specifically, with an internalization that for tumor cells was of two orders of magnitude higher after 3 h and up to three orders of magnitude higher after 24 h. Overall it was observed a greater internationalization for MM NPs externally decorated with HA. These data indicated that the NPs produced with the MM having better performing technological features in terms of the stability and homogeneity of the dimensions and PDI had a superior efficiency of the interaction with cell membranes 43 .…”

“…These data indicated that the NPs produced with the MM have better performing technological features in terms of the stability and homogeneity of the dimensions, and PDI has a superior efficiency of interaction with the cell membranes. 43…”

“…These data indicated that the NPs produced with the MM have better performing technological features in terms of the stability and homogeneity of the dimensions, and PDI has a superior efficiency of interaction with the cell membranes. 43 Conclusions IRI-loaded HA-based NPs based on the nanoprecipitation with a subsequent solvent evaporation process was developed by means of new technology named microfluidic method and compared with those fabricated by traditional bulk method, respectively. To the best of our knowledge, this is the first example of hyaluronic acid/PLGA core-shell nanoparticles, without any polymer chemical modifications, based only on their electrostatic interactions driven by lipophilicity gradient, fabricated by the microfluidic method.…”

Hyaluronic Acid Modified Nanostructured Lipid Carrier for Targeting Delivery of Kaempferol to NSCLC: Preparation, Optimization, Characterization, and Performance Evaluation In Vitro

“…As a result, HA was chosen as the targeted factor for treatment based on the pathological features of NSCLC cells, hence improving therapeutic effectiveness and lowering systemic toxicity. Since different molecular weights of HA possess diverse biological activities [ 38 ], we considered whether different molecular weights of HA have varied targeting effects. With this in mind, we modified HA with two distinct molecular weights and compared the in vitro antitumor effects in this investigation.…”

Supramolecular Functionalisation of B/N Co-Doped Carbon Nano-Onions for Novel Nanocarrier Systems

“…Besides its dispersant properties, HA is used for its targetability [ 21 , 22 , 23 ]. HA acts as a targeting ligand towards cancer cells overexpressing the hyaluronate (CD44) receptor [ 24 ]. Furthermore, HA can avoid the adsorption of many blood proteins, prevent coagulation, and prolong the half-life of HA-decorated nanoparticles in the circulatory system [ 25 ].…”