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

Pharmaceuticals

Rossella Dorati¹  Bice Conti¹  Antonietta Greco¹  Tiziana Modena¹  Ida Genta¹  Federica Riva²  Enrica Chiesa³ 

[1] Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy;Department of Public Health, Experimental and Forensic Medicine, Histology and Embryology Unit, University of Pavia, 27100 Pavia, Italy;Department of Surgery, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy;

关键词: hyaluronic acid;    CD44 targeting;    microfluidic;    nanoparticles;    endocytic mechanism;    transport inhibitors;   

DOI  :  10.3390/ph15010103

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown