{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T02:12:45Z","timestamp":1793326365262,"version":"4.5.0"},"reference-count":126,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T00:00:00Z","timestamp":1601337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2019R1A2B5B03100464"],"award-info":[{"award-number":["2019R1A2B5B03100464"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2019M3E5D5066525"],"award-info":[{"award-number":["2019M3E5D5066525"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["20100027955"],"award-info":[{"award-number":["20100027955"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2018R1A2B3006080"],"award-info":[{"award-number":["2018R1A2B3006080"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2019R1A6A1A11051471"],"award-info":[{"award-number":["2019R1A6A1A11051471"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Owing to their unique biological functions, hyaluronic acid (HA) and its derivatives have been explored extensively for biomedical applications such as tissue engineering, drug delivery, and molecular imaging. In particular, self-assembled HA nanoparticles (HA-NPs) have been used widely as target-specific and long-acting nanocarriers for the delivery of a wide range of therapeutic or diagnostic agents. Recently, it has been demonstrated that empty HA-NPs without bearing any therapeutic agent can be used therapeutically for the treatment of inflammatory diseases via modulating inflammatory responses. In this review, we aim to provide an overview of the significant achievements in this field and highlight the potential of HA-NPs for the treatment of inflammatory diseases.<\/jats:p>","DOI":"10.3390\/pharmaceutics12100931","type":"journal-article","created":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T20:56:22Z","timestamp":1601412982000},"page":"931","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Hyaluronic Acid Nanoparticles as Nanomedicine for Treatment of Inflammatory Diseases"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8534-7158","authenticated-orcid":false,"given":"N.Vijayakameswara","family":"Rao","sequence":"first","affiliation":[{"name":"School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Korea"},{"name":"Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei 10617, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Gi","family":"Rho","sequence":"additional","affiliation":[{"name":"Department of Molecular Science &amp; Technology, Ajou University, Suwon 16499, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2479-0783","authenticated-orcid":false,"given":"Wooram","family":"Um","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pramod Kumar","family":"EK","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5952-0700","authenticated-orcid":false,"given":"Van Quy","family":"Nguyen","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byeong Hoon","family":"Oh","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7701-4684","authenticated-orcid":false,"given":"Wook","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Molecular Science &amp; Technology, Ajou University, Suwon 16499, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Hyung","family":"Park","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Korea"},{"name":"Department Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,29]]},"reference":[{"key":"ref_1","first-page":"2115","article-title":"Use of oily contrast medium for selective drug targeting to tumor: Enhanced therapeutic effect and X-ray image","volume":"44","author":"Iwai","year":"1984","journal-title":"Cancer Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/nrd2591","article-title":"Strategies in the design of nanoparticles for therapeutic applications","volume":"9","author":"Petros","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.ijpharm.2005.10.010","article-title":"Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles","volume":"307","author":"Owens","year":"2006","journal-title":"Int. J. Pharm."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1016\/j.addr.2008.08.005","article-title":"Active targeting schemes for nanoparticle systems in cancer therapeutics","volume":"60","author":"Byrne","year":"2008","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1002\/adfm.200801655","article-title":"New generation of multifunctional nanoparticles for cancer imaging and therapy","volume":"19","author":"Park","year":"2009","journal-title":"Adv. Funct. Mater."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nmat2614","article-title":"Emerging applications of stimuli-responsive polymer materials","volume":"9","author":"Stuart","year":"2010","journal-title":"Nat. Mater."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.jconrel.2008.04.024","article-title":"Super pH-sensitive multifunctional polymeric micelle for tumor pHe specific TAT exposure and multidrug resistance","volume":"129","author":"Lee","year":"2008","journal-title":"J. Control. Release"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2846","DOI":"10.1002\/ange.200705240","article-title":"A near-infrared-fluorescence-quenched gold-nanoparticle imaging probe for in vivo drug screening and protease activity determination","volume":"120","author":"Lee","year":"2008","journal-title":"Angew. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1806380","DOI":"10.1002\/adma.201806380","article-title":"Biologically inspired, cell-selective release of aptamer-trapped growth factors by traction forces","volume":"31","author":"Oliva","year":"2019","journal-title":"Adv. Mater."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.biomaterials.2016.06.044","article-title":"In situ diselenide-crosslinked polymeric micelles for ROS-mediated anticancer drug delivery","volume":"103","author":"Deepagan","year":"2016","journal-title":"Biomaterials"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"9616","DOI":"10.1039\/C8NR00888D","article-title":"ROS-responsive mesoporous silica nanoparticles for MR imaging-guided photodynamically maneuvered chemotherapy","volume":"10","author":"Rao","year":"2018","journal-title":"Nanoscale"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"110","DOI":"10.3389\/fbioe.2018.00110","article-title":"Recent progress and advances in stimuli-responsive polymers for cancer therapy","volume":"6","author":"Rao","year":"2018","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.colsurfb.2011.10.029","article-title":"Hyaluronic acid-based nanocarriers for intracellular targeting: Interfacial interactions with proteins in cancer","volume":"99","author":"Choi","year":"2012","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Stern, R. (2008). Hyaluronidases in cancer biology. Hyaluronan in Cancer Biology, Elsevier.","DOI":"10.1016\/B978-012374178-3.10012-2"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1021\/cr050247k","article-title":"Hyaluronidases: Their genomics, structures, and mechanisms of action","volume":"106","author":"Stern","year":"2006","journal-title":"Chem. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1021\/bm050867v","article-title":"Degradative action of reactive oxygen species on hyaluronan","volume":"7","author":"Mendichi","year":"2006","journal-title":"Biomacromolecules"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1803549","DOI":"10.1002\/adma.201803549","article-title":"Hyaluronic acid\u2013Based activatable nanomaterials for stimuli-responsive imaging and therapeutics: Beyond CD44-mediated drug delivery","volume":"31","author":"Choi","year":"2019","journal-title":"Adv. Mater."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.1016\/j.biomaterials.2010.11.010","article-title":"PEGylation of hyaluronic acid nanoparticles improves tumor targetability in vivo","volume":"32","author":"Choi","year":"2011","journal-title":"Biomaterials"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1097\/WNR.0b013e328355380e","article-title":"Osteopontin is upregulated after mechanical brain injury and stimulates neurite growth from hippocampal neurons through \u03b21 integrin and CD44","volume":"23","author":"Plantman","year":"2012","journal-title":"Neuroreport"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.matbio.2006.08.261","article-title":"Hyaluronan-mediated angiogenesis in vascular disease: Uncovering RHAMM and CD44 receptor signaling pathways","volume":"26","author":"Slevin","year":"2007","journal-title":"Matrix Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/B978-0-12-800092-2.00008-3","article-title":"HAS2 and CD44 in breast tumorigenesis","volume":"Volume 123","author":"Heldin","year":"2014","journal-title":"Advances in Cancer Research"},{"key":"ref_22","first-page":"133","article-title":"Doxorubicin-loaded dual-functional hyaluronic acid nanoparticles: Preparation, characterization and antitumor efficacy in vitro and in vivo","volume":"19","author":"Tian","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3456","DOI":"10.1080\/21691401.2019.1626863","article-title":"Hyaluronic acid-modified selenium nanoparticles for enhancing the therapeutic efficacy of paclitaxel in lung cancer therapy","volume":"47","author":"Zou","year":"2019","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1208\/s12249-020-01764-3","article-title":"Lipid\/hyaluronic acid\u2013Coated Doxorubicin-Fe3O4 as a dual-targeting nanoparticle for enhanced cancer therapy","volume":"21","author":"Liang","year":"2020","journal-title":"AAPS Pharmscitech"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"111279","DOI":"10.1016\/j.colsurfb.2020.111279","article-title":"Catechol-modified chitosan\/hyaluronic acid nanoparticles as a new avenue for local delivery of doxorubicin to oral cancer cells","volume":"196","author":"Pornpitchanarong","year":"2020","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/nrc3254","article-title":"Multitasking hyaluronic acid","volume":"12","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5861","DOI":"10.1039\/C9TB01250H","article-title":"Hyaluronic acid modified doxorubicin loaded Fe3O4 nanoparticles effectively inhibit breast cancer metastasis","volume":"7","author":"Gong","year":"2019","journal-title":"J. Mater. Chem. B"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"S152","DOI":"10.1097\/01.blo.0000143804.26638.82","article-title":"Hyaluronan and CD44: Modulators of chondrocyte metabolism","volume":"427","author":"Knudson","year":"2004","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_29","first-page":"2604","article-title":"Therapeutic potential of hyaluronic acid\/chitosan nanoparticles for the delivery of curcuminoid in knee osteoarthritis and an in vitro evaluation in chondrocytes","volume":"42","author":"Wang","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0945-053X(01)00184-6","article-title":"Hyaluronan and its catabolic products in tissue injury and repair","volume":"21","author":"Noble","year":"2002","journal-title":"Matrix Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.3389\/fphar.2020.01199","article-title":"Attenuation of Radiation-Induced Lung Injury by Hyaluronic Acid Nanoparticles","volume":"11","author":"Lierova","year":"2020","journal-title":"Front. Pharm."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Pandolfi, L., Frangipane, V., Bocca, C., Marengo, A., Tarro Genta, E., Bozzini, S., Morosini, M., D\u2019Amato, M., Vitulo, S., and Monti, M. (2019). Hyaluronic acid\u2013decorated liposomes as innovative targeted delivery system for lung fibrotic cells. Molecules, 24.","DOI":"10.3390\/molecules24183291"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1111\/wrr.12214","article-title":"Hyaluronan in wound healing: Rediscovering a major player","volume":"22","author":"Aya","year":"2014","journal-title":"Wound Repair Regen."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.carbpol.2018.11.085","article-title":"Electrospinning in water and in situ crosslinking of hyaluronic acid\/cyclodextrin nanofibers: Towards wound dressing with controlled drug release","volume":"207","author":"Couffin","year":"2019","journal-title":"Carbohydr. Polym."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Moretto, P., Karousou, E., Viola, M., Caon, I., D\u2019Angelo, M.L., De Luca, G., Passi, A., and Vigetti, D. (2015). Regulation of hyaluronan synthesis in vascular diseases and diabetes. J. Diabetes Res.","DOI":"10.1155\/2015\/167283"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.matlet.2016.10.117","article-title":"Oral delivery of insulin using CaCO3-based composite nanocarriers with hyaluronic acid coatings","volume":"188","author":"Liu","year":"2017","journal-title":"Mater. Lett."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/S0955-0674(00)00135-6","article-title":"Hyaluronan: A multifunctional, megaDalton, stealth molecule","volume":"12","author":"Lee","year":"2000","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s13205-016-0379-9","article-title":"Biotechnological production of hyaluronic acid: A mini review","volume":"6","author":"Sze","year":"2016","journal-title":"3 Biotech"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1186\/1475-2859-10-99","article-title":"Microbial production of hyaluronic acid: Current state, challenges, and perspectives","volume":"10","author":"Liu","year":"2011","journal-title":"Microb. Cell Fact."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.jconrel.2018.04.015","article-title":"Hyaluronic acid-based biopharmaceutical delivery and tumor-targeted drug delivery system","volume":"278","author":"Huang","year":"2018","journal-title":"J. Control. Release"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.carbpol.2017.10.054","article-title":"The role of hydrophobic modification on hyaluronic acid dynamics and self-assembly","volume":"182","author":"Payne","year":"2018","journal-title":"Carbohydr. Polym."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1096\/fasebj.6.7.1563592","article-title":"Hyaluronan 1","volume":"6","author":"Laurent","year":"1992","journal-title":"FASEB J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"25085","DOI":"10.1074\/jbc.274.35.25085","article-title":"Three isoforms of mammalian hyaluronan synthases have distinct enzymatic properties","volume":"274","author":"Itano","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/j.carres.2005.01.022","article-title":"Experimental approaches to hyaluronan structure","volume":"340","author":"Cowman","year":"2005","journal-title":"Carbohydr. Res."},{"key":"ref_45","first-page":"1867","article-title":"Morphology and ultrastructure of human vitreous fibers","volume":"30","author":"Sebag","year":"1989","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1002\/art.1780330605","article-title":"Inflammation and cartilage metabolism in rheumatoid arthritis. Studies of the blood markers hyaluronic acid, orosomucoid, and keratan sulfate","volume":"33","author":"Poole","year":"1990","journal-title":"Arthritis Rheumatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-12-800092-2.00001-0","article-title":"Emerging roles for hyaluronidase in cancer metastasis and therapy","volume":"Volume 123","author":"McAtee","year":"2014","journal-title":"Advances in Cancer Research"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/(SICI)1097-0215(19971104)73:3<327::AID-IJC4>3.0.CO;2-1","article-title":"Increased hyaluronidase levels in breast tumor metastases","volume":"73","author":"Bertrand","year":"1997","journal-title":"Int. J. Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.yexcr.2005.07.026","article-title":"The over-expression of HAS2, Hyal-2 and CD44 is implicated in the invasiveness of breast cancer","volume":"310","author":"Udabage","year":"2005","journal-title":"Exp. Cell Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1016\/0092-8674(90)90694-A","article-title":"CD44 is the principal cell surface receptor for hyaluronate","volume":"61","author":"Aruffo","year":"1990","journal-title":"Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1242\/jcs.00407","article-title":"TSG-6: A multifunctional protein associated with inflammation","volume":"116","author":"Milner","year":"2003","journal-title":"J. Cell Sci."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Harris, E.N., and Baker, E. (2020). Role of the Hyaluronan Receptor, Stabilin-2\/HARE, in Health and Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21103504"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"10582","DOI":"10.1021\/jf8017029","article-title":"Absorption, uptake and tissue affinity of high-molecular-weight hyaluronan after oral administration in rats and dogs","volume":"56","author":"Balogh","year":"2008","journal-title":"J. Agric. Food Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1089\/15396850360495718","article-title":"Metabolism of macromolecules in tissue","volume":"1","author":"Liu","year":"2003","journal-title":"Lymphat. Res. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1042\/bj2000415","article-title":"Plasma clearance, tissue distribution and metabolism of hyaluronic acid injected intravenously in the rabbit","volume":"200","author":"Fraser","year":"1981","journal-title":"Biochem. J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/BF03191112","article-title":"The effect of molecular weight on the biodistribution of hyaluronic acid radiolabeled with 111 In after intravenous administration to rats","volume":"33","author":"Svanovsky","year":"2008","journal-title":"Eur. J. Drug Metab. Pharm."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/j.1440-1681.1984.tb00235.x","article-title":"Elimination of hyaluronic acid from the blood stream in the human","volume":"11","author":"Fraser","year":"1984","journal-title":"Clin. Exp. Pharm. Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1021\/acsbiomaterials.9b00295","article-title":"Hyaluronic Acid nanoparticle composite films confer favorable time-dependent biofunctions for vascular wound healing","volume":"5","author":"Jiang","year":"2019","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1177\/0885328220905256","article-title":"Tumor-targeting and redox-sensitive micelles based on hyaluronic acid conjugate for delivery of paclitaxel","volume":"34","author":"Liu","year":"2020","journal-title":"J. Biomater. Appl."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1517\/17425247.2016.1112374","article-title":"Recent developments in hyaluronic acid-based nanomedicine for targeted cancer treatment","volume":"13","author":"Rao","year":"2016","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.ijbiomac.2019.03.030","article-title":"Enzyme and pH dual-responsive hyaluronic acid nanoparticles mediated combination of photodynamic therapy and chemotherapy","volume":"130","author":"Ren","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1039\/C7TB03068A","article-title":"Hybrid nanoparticles based on chlorin e6-conjugated hyaluronic acid\/poly (l-histidine) copolymer for theranostic application to tumors","volume":"6","author":"Lee","year":"2018","journal-title":"J. Mater. Chem. B"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2310","DOI":"10.1016\/j.biomaterials.2011.11.022","article-title":"Redox-sensitive micelles self-assembled from amphiphilic hyaluronic acid-deoxycholic acid conjugates for targeted intracellular delivery of paclitaxel","volume":"33","author":"Li","year":"2012","journal-title":"Biomaterials"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1021\/bc8000485","article-title":"Hyaluronic acid\u2212paclitaxel conjugate micelles: Synthesis, characterization, and antitumor activity","volume":"19","author":"Lee","year":"2008","journal-title":"Bioconjugate Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.biomaterials.2009.09.030","article-title":"Self-assembled hyaluronic acid nanoparticles for active tumor targeting","volume":"31","author":"Choi","year":"2010","journal-title":"Biomaterials"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4102","DOI":"10.1039\/b900456d","article-title":"Self-assembled hyaluronic acid nanoparticles as a potential drug carrier for cancer therapy: Synthesis, characterization, and in vivo biodistribution","volume":"19","author":"Choi","year":"2009","journal-title":"J. Mater. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"5785","DOI":"10.1021\/acsnano.7b01385","article-title":"Hyaluronan Nanoparticles Selectively Target Plaque-Associated Macrophages and Improve Plaque Stability in Atherosclerosis","volume":"11","author":"Beldman","year":"2017","journal-title":"ACS Nano"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1517\/17425241003730399","article-title":"Nanostructured hyaluronic acid-based materials for active delivery to cancer","volume":"7","author":"Ossipov","year":"2010","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Chiesa, E., Riva, F., Dorati, R., Greco, A., Ricci, S., Pisani, S., Patrini, M., Modena, T., Conti, B., and Genta, I. (2020). On-Chip synthesis of hyaluronic acid-based nanoparticles for selective inhibition of cd44+ human mesenchymal stem cell proliferation. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12030260"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"45121","DOI":"10.1038\/srep45121","article-title":"Hybrid Core-Shell (HyCoS) nanoparticles produced by complex coacervation for multimodal applications","volume":"7","author":"Vecchione","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.ijpharm.2012.07.011","article-title":"Exploring the assembly process and properties of novel crosslinker-free hyaluronate-based polyelectrolyte complex nanocarriers","volume":"436","author":"Umerska","year":"2012","journal-title":"Int. J. Pharm."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1007\/s13233-013-1171-x","article-title":"Tumor targeting and pH-responsive polyelectrolyte complex nanoparticles based on hyaluronic acid-paclitaxel conjugates and chitosan for oral delivery of paclitaxel","volume":"21","author":"Li","year":"2013","journal-title":"Macromol. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1016\/j.ijbiomac.2017.04.105","article-title":"Nanoparticles based on chitosan hydrochloride\/hyaluronic acid\/PEG containing curcumin: In vitro evaluation and pharmacokinetics in rats","volume":"102","author":"Xu","year":"2017","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.ijbiomac.2018.02.128","article-title":"Chitosan hydrochloride\/hyaluronic acid nanoparticles coated by mPEG as long-circulating nanocarriers for systemic delivery of mitoxantrone","volume":"113","author":"Wang","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"7996","DOI":"10.1039\/c1jm10466g","article-title":"Mineralized hyaluronic acid nanoparticles as a robust drug carrier","volume":"21","author":"Han","year":"2011","journal-title":"J. Mater. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1039\/C2NR32145A","article-title":"Hyaluronic acid modified mesoporous silica nanoparticles for targeted drug delivery to CD44-overexpressing cancer cells","volume":"5","author":"Yu","year":"2013","journal-title":"Nanoscale"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1046\/j.1365-2796.1997.00170.x","article-title":"Hyaluronan: Its nature, distribution, functions and turnover","volume":"242","author":"Fraser","year":"1997","journal-title":"J. Intern. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1146\/annurev.cellbio.23.090506.123337","article-title":"Hyaluronan in tissue injury and repair","volume":"23","author":"Jiang","year":"2007","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1126\/science.1069659","article-title":"Resolution of lung inflammation by CD44","volume":"296","author":"Teder","year":"2002","journal-title":"Science"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/j.ejcb.2006.05.009","article-title":"Hyaluronan fragments: An information-rich system","volume":"85","author":"Stern","year":"2006","journal-title":"Eur. J. Cell Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"43094","DOI":"10.1074\/jbc.M112.349209","article-title":"The high and low molecular weight forms of hyaluronan have distinct effects on CD44 clustering","volume":"287","author":"Yang","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"5369","DOI":"10.1016\/j.biomaterials.2013.03.065","article-title":"Hyaluronic acid (HA) presentation as a tool to modulate and control the receptor-mediated uptake of HA-coated nanoparticles","volume":"34","author":"Almalik","year":"2013","journal-title":"Biomaterials"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.jconrel.2018.04.006","article-title":"Self-assembled hyaluronic acid nanoparticles: Implications as a nanomedicine for treatment of type 2 diabetes","volume":"279","author":"Rho","year":"2018","journal-title":"J. Control. Release"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"7260","DOI":"10.1016\/j.biomaterials.2005.05.044","article-title":"Therapeutic potential of nanoparticulate systems for macrophage targeting","volume":"26","author":"Chellat","year":"2005","journal-title":"Biomaterials"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S1462399401003696","article-title":"Atherosclerosis: Role of chemokines and macrophages","volume":"3","author":"Lucas","year":"2001","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1073\/pnas.0606281104","article-title":"Detecting and assessing macrophages in vivo to evaluate atherosclerosis noninvasively using molecular MRI","volume":"104","author":"Amirbekian","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0168-3659(01)00549-1","article-title":"Targeting to macrophages: Role of physicochemical properties of particulate carriers\u2014liposomes and microspheres\u2014on the phagocytosis by macrophages","volume":"79","author":"Ahsan","year":"2002","journal-title":"J. Control. Release"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S0065-230X(08)60101-3","article-title":"CD44: Structure, function and association with the malignant process","volume":"Volume 71","author":"Naor","year":"1997","journal-title":"Advances in Cancer Research"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.1021\/bc100354m","article-title":"Hyaluronic acid immobilized magnetic nanoparticles for active targeting and imaging of macrophages","volume":"21","author":"Kamat","year":"2010","journal-title":"Bioconjugate Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"101","DOI":"10.3389\/fimmu.2014.00101","article-title":"Hyaluronan, a crucial regulator of inflammation","volume":"5","author":"Petrey","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/s00424-007-0212-8","article-title":"The endothelial glycocalyx: Composition, functions, and visualization","volume":"454","author":"Reitsma","year":"2007","journal-title":"Pflug. Arch."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"253","DOI":"10.4161\/derm.21923","article-title":"Hyaluronic acid: A key molecule in skin aging","volume":"4","author":"Papakonstantinou","year":"2012","journal-title":"Dermato-endocrinology"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1089\/jir.2008.0027","article-title":"Monocyte chemoattractant protein-1 (MCP-1): An overview","volume":"29","author":"Deshmane","year":"2009","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"182","DOI":"10.3389\/fimmu.2015.00182","article-title":"The role of CD44 in disease pathophysiology and targeted treatment","volume":"6","author":"Jordan","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"867","DOI":"10.2337\/db14-0149","article-title":"Anti-CD44 antibody treatment lowers hyperglycemia and improves insulin resistance, adipose inflammation, and hepatic steatosis in diet-induced obese mice","volume":"64","author":"Kodama","year":"2015","journal-title":"Diabetes"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"7049","DOI":"10.1073\/pnas.1114513109","article-title":"Expression-based genome-wide association study links the receptor CD44 in adipose tissue with type 2 diabetes","volume":"109","author":"Kodama","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1002\/ijc.2910600511","article-title":"The role of hyaluronan in tumour neovascularization","volume":"60","author":"Rooney","year":"1995","journal-title":"Int. J. Cancer"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.jconrel.2009.09.010","article-title":"Target specific and long-acting delivery of protein, peptide, and nucleotide therapeutics using hyaluronic acid derivatives","volume":"141","author":"Oh","year":"2010","journal-title":"J. Control. Release"},{"key":"ref_99","first-page":"2368","article-title":"Hyaluronate activation of CD44 induces insulin-like growth factor-1 expression by a tumor necrosis factor-alpha-dependent mechanism in murine macrophages","volume":"91","author":"Noble","year":"1993","journal-title":"J. Clin."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1101\/gad.13.1.35","article-title":"Localization of matrix metalloproteinase 9 to the cell surface provides a mechanism for CD44-mediated tumor invasion","volume":"13","author":"Yu","year":"1999","journal-title":"Genes Dev."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1126\/science.1142382","article-title":"A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants","volume":"316","author":"Scott","year":"2007","journal-title":"Science"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1007\/s11095-014-1602-1","article-title":"Cluster of differentiation 44 targeted hyaluronic acid based nanoparticles for MDR1 siRNA delivery to overcome drug resistance in ovarian cancer","volume":"32","author":"Yang","year":"2015","journal-title":"Pharm. Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/nrd4275","article-title":"Targeting inflammation in the treatment of type 2 diabetes: Time to start","volume":"13","author":"Donath","year":"2014","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1007\/s00125-015-3603-y","article-title":"The receptor CD44 is associated with systemic insulin resistance and proinflammatory macrophages in human adipose tissue","volume":"58","author":"Liu","year":"2015","journal-title":"Diabetologia"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"116161","DOI":"10.1016\/j.carbpol.2020.116161","article-title":"Self-assembled hyaluronic acid nanoparticle suppresses fat accumulation via CD44 in diet-induced obese mice","volume":"237","author":"Lee","year":"2020","journal-title":"Carbohydr. Polym."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"107477","DOI":"10.1016\/j.pharmthera.2020.107477","article-title":"The therapeutic potential of second and third generation CB1R antagonists","volume":"208","author":"Cinar","year":"2020","journal-title":"Pharmacol. Ther."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1111\/dom.13350","article-title":"Peripheral cannabinoid 1 receptor blockade mitigates adipose tissue inflammation via NLRP3 inflammasome in mouse models of obesity","volume":"20","author":"Han","year":"2018","journal-title":"Diabetes Obes. Metab"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"4314","DOI":"10.1096\/fj.201801152RR","article-title":"A novel peripheral cannabinoid 1 receptor antagonist, AJ5012, improves metabolic outcomes and suppresses adipose tissue inflammation in obese mice","volume":"33","author":"Han","year":"2019","journal-title":"FASEB J."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1038\/nm.2538","article-title":"Atherosclerosis: Current pathogenesis and therapeutic options","volume":"17","author":"Weber","year":"2011","journal-title":"Nat. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1161\/ATVBAHA.109.187518","article-title":"Structure and function of HDL mimetics","volume":"30","author":"Navab","year":"2010","journal-title":"Atertio. Thromb. Vasc. Biol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/nrd3578","article-title":"Perspectives and opportunities for nanomedicine in the management of atherosclerosis","volume":"10","author":"Lobatto","year":"2011","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1038\/nrd2115","article-title":"Angiogenesis: An organizing principle for drug discovery?","volume":"6","author":"Folkman","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"718","DOI":"10.3181\/00379727-72-17555","article-title":"Effect of cortisone on production of granulation tissue in the rabbit","volume":"72","author":"Ragan","year":"1949","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/175435a0","article-title":"Biosynthesis of hyaluronate","volume":"175","author":"Lowther","year":"1955","journal-title":"Nature"},{"key":"ref_115","first-page":"485","article-title":"The production of capsules, hyaluronic acid and hyaluronidase by 25 strains of group C streptococci","volume":"15","author":"Maclennan","year":"1956","journal-title":"Microbiology"},{"key":"ref_116","first-page":"321","article-title":"Pasteurellosis: Pasteurella multocida and Pasteurella hemolytica","volume":"11","author":"Carter","year":"1967","journal-title":"Adv. Vet. Sci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.biomaterials.2015.02.089","article-title":"Hyaluronic acid nanoparticles for active targeting atherosclerosis","volume":"53","author":"Lee","year":"2015","journal-title":"Biomaterials"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"786","DOI":"10.2174\/092986708783955554","article-title":"Hyaluronic acid: Targeting immune modulatory components of the extracellular matrix in atherosclerosis","volume":"15","author":"Bot","year":"2008","journal-title":"Curr. Med. Chem."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Shin, J.M., Choi, G.H., Song, S.H., Ko, H., Lee, E.S., Lee, J.A., Yoo, P.J., and Park, J.H. (2019). Metal-phenolic network-coated hyaluronic acid nanoparticles for ph-responsive drug delivery. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11120636"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"26870","DOI":"10.1021\/acsami.8b06848","article-title":"Intracellular NO-releasing hyaluronic acid-based nanocarriers: A potential chemosensitizing agent for cancer chemotherapy","volume":"10","author":"Kim","year":"2018","journal-title":"Acs Appl. Mater. Interfaces"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"7632","DOI":"10.1039\/c4cc02595d","article-title":"A hyaluronic acid\u2013methotrexate conjugate for targeted therapy of rheumatoid arthritis","volume":"50","author":"Shin","year":"2014","journal-title":"Chem. Commun."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.jconrel.2017.03.012","article-title":"Endogenous inspired biomineral-installed hyaluronan nanoparticles as pH-responsive carrier of methotrexate for rheumatoid arthritis","volume":"252","author":"Alam","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"11849","DOI":"10.1166\/jnn.2016.13606","article-title":"pH-Responsive hyaluronic acid-based nanocarrier for treatment of rheumatoid arthritis","volume":"16","author":"Jeon","year":"2016","journal-title":"J. Nanosci. Nanotechnol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.jconrel.2014.07.057","article-title":"Hyaluronan nanoparticles bearing \u03b3-secretase inhibitor: In vivo therapeutic effects on rheumatoid arthritis","volume":"192","author":"Heo","year":"2014","journal-title":"J. Control. Release"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s40005-019-00448-w","article-title":"Recent progresses in the development of hyaluronic acid-based nanosystems for tumor-targeted drug delivery and cancer imaging","volume":"50","author":"Cho","year":"2020","journal-title":"J. Pharm. Investig."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"2889","DOI":"10.1021\/acs.biomac.9b00564","article-title":"Hyaluronic acid derivatives for translational medicines","volume":"20","author":"Kim","year":"2019","journal-title":"Biomacromolecules"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/12\/10\/931\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:15:00Z","timestamp":1760177700000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/12\/10\/931"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,29]]},"references-count":126,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["pharmaceutics12100931"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics12100931","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,29]]}}}