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Multifunctional Hyaluronic Acid and Chondroitin Sulfate Nanoparticles: Impact of Glycosaminoglycan Presentation on Receptor Mediated Cellular Uptake and Immune Activation
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry. Tampere Univ Technol, BioMediTech Inst Biosci & Med Technol, Bioengn & Nanomed Grp, Tampere 33520, Finland..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
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2016 (English)In: ACS Applied Materials and Interfaces, ISSN 1944-8244, E-ISSN 1944-8252, Vol. 8, no 32, 20614-20624 p.Article in journal (Refereed) Published
Abstract [en]

Hyaluronic acid (HA) and chondroitin sulfate (CS) polymers are extensively used for various biomedical applications, such as for tissue engineering, drug delivery, and gene delivery. Although both these biopolymers are known to target cell surface CD44 receptors, their relative cellular targeting properties and immune activation potential have never been evaluated. In this article, we present the synthesis and characterization of novel self assembled supramolecular HA and CS nanoparticles (NPs). These NPs were developed using fluorescein as a hydrophobic component that induced amphiphilicity in biopolymers and also efficiently stabilized anticancer drug doxorubicin (DOX) promoting a near zero-order drug release. The cellular uptake and cytotoxicity studies of these NPs in different human cancer lines, namely, human colorectal carcinoma cell line HCT116 and human breast cancer cell line MCF-7 demonstrated dose dependent cytotoxicity. Interestingly, both NPs showed CD44 dependent cellular uptake with the CS DOX NP displaying higher dose-dependent cytotoxicity than the HA DOX NP in different mammalian cells tested. Immunological evaluation of these nanocarriers in an ex vivo human whole blood model revealed that unlike unmodified polymers, the HA NP and CS NP surprisingly showed platelet aggregation and thrombin antithrombin complex formation at high concentrations (0.8 mg/mL). We also observed a clear difference in early- and late-stage complement activation (C3a and sC5b-9) with CS and CS NP triggering significant complement activation at high concentrations (0.08-0.8 mg/mL), unlike HA and HA NP. These results offer new insight into designing glycosaminoglycan-based NPs and understanding their hematological responses and targeting ability.

Place, publisher, year, edition, pages
2016. Vol. 8, no 32, 20614-20624 p.
Keyword [en]
Hyaluronic acid, chondroitin sulfate, nanoparticles, cancer, immune activation, drug delivery
National Category
Immunology in the medical area
Identifiers
URN: urn:nbn:se:uu:diva-303274DOI: 10.1021/acsami.6b06823ISI: 000381715900013PubMedID: 27468113OAI: oai:DiVA.org:uu-303274DiVA: diva2:971364
Funder
EU, European Research Council, 602699
Available from: 2016-09-16 Created: 2016-09-15 Last updated: 2016-09-16Bibliographically approved

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Oommen, Oommen PodiyanNilsson, BoHilborn, JönsVarghese, Oommen P.
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