Hyaluronic acid nanogels with enzyme-sensitive cross-linking group for drug delivery

A methacrylation strategy was employed to functionalize hyaluronic acid and prepare hyaluronic acid (HA) nanogels. Dynamic light scattering, zeta potential analyzer and electron microscopy were utilized to characterize the nanogels and their enzyme-degradability in vitro. It was found that these nan...

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Veröffentlicht in:Journal of controlled release 2015-05, Vol.205, p.206-217
Hauptverfasser: Yang, Chenchen, Wang, Xin, Yao, Xikuang, Zhang, Yajun, Wu, Wei, Jiang, Xiqun
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creator Yang, Chenchen
Wang, Xin
Yao, Xikuang
Zhang, Yajun
Wu, Wei
Jiang, Xiqun
description A methacrylation strategy was employed to functionalize hyaluronic acid and prepare hyaluronic acid (HA) nanogels. Dynamic light scattering, zeta potential analyzer and electron microscopy were utilized to characterize the nanogels and their enzyme-degradability in vitro. It was found that these nanogels had a spherical morphology with the diameter of about 70nm, and negative surface potential. When doxorubicin (DOX) was loaded into the nanogels, the diameter decreased to approximately 50nm with a drug loading content of 16% and encapsulation efficiency of 62%. Cellular uptake examinations showed that HA nanogels could be preferentially internalized by two-dimensional (2D) cells and three-dimensional (3D) multicellular spheroids (MCs) which both overexpress CD44 receptor. Near-infrared fluorescence imaging, biodistribution and penetration examinations in tumor tissue indicated that the HA nanogels could efficiently accumulate and penetrate the tumor matrix. In vivo antitumor evaluation found that DOX-loaded HA nanogels exhibited a significantly superior antitumor effect. Doxorubicin-loaded hyaluronic acid nanogels were synthesized by a methacrylated strategy. In vitro cellular uptake shows that these nanogels were preferentially internalized by the CD44 or CD168-overexpressed cancer cells. In vivo antitumor examination indicates that these nanogels suppress tumor growth distinctly. [Display omitted]
doi_str_mv 10.1016/j.jconrel.2015.02.008
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Dynamic light scattering, zeta potential analyzer and electron microscopy were utilized to characterize the nanogels and their enzyme-degradability in vitro. It was found that these nanogels had a spherical morphology with the diameter of about 70nm, and negative surface potential. When doxorubicin (DOX) was loaded into the nanogels, the diameter decreased to approximately 50nm with a drug loading content of 16% and encapsulation efficiency of 62%. Cellular uptake examinations showed that HA nanogels could be preferentially internalized by two-dimensional (2D) cells and three-dimensional (3D) multicellular spheroids (MCs) which both overexpress CD44 receptor. Near-infrared fluorescence imaging, biodistribution and penetration examinations in tumor tissue indicated that the HA nanogels could efficiently accumulate and penetrate the tumor matrix. In vivo antitumor evaluation found that DOX-loaded HA nanogels exhibited a significantly superior antitumor effect. Doxorubicin-loaded hyaluronic acid nanogels were synthesized by a methacrylated strategy. In vitro cellular uptake shows that these nanogels were preferentially internalized by the CD44 or CD168-overexpressed cancer cells. In vivo antitumor examination indicates that these nanogels suppress tumor growth distinctly. 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Doxorubicin-loaded hyaluronic acid nanogels were synthesized by a methacrylated strategy. In vitro cellular uptake shows that these nanogels were preferentially internalized by the CD44 or CD168-overexpressed cancer cells. In vivo antitumor examination indicates that these nanogels suppress tumor growth distinctly. 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Wang, Xin ; Yao, Xikuang ; Zhang, Yajun ; Wu, Wei ; Jiang, Xiqun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c435t-e73110b43e7438c3bd1b1ab7fbafb80c7903501582d55691dac4f672cd562f123</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Antibiotics, Antineoplastic - chemistry</topic><topic>Antibiotics, Antineoplastic - metabolism</topic><topic>Antibiotics, Antineoplastic - pharmacology</topic><topic>Cell Survival - drug effects</topic><topic>Chemistry, Pharmaceutical</topic><topic>Dose-Response Relationship, Drug</topic><topic>Doxorubicin - chemistry</topic><topic>Doxorubicin - metabolism</topic><topic>Doxorubicin - pharmacology</topic><topic>Drug Carriers</topic><topic>Drug delivery</topic><topic>Gels</topic><topic>Hep G2 Cells</topic><topic>Humans</topic><topic>Hyaluronan Receptors - metabolism</topic><topic>Hyaluronic Acid - analogs &amp; derivatives</topic><topic>Hyaluronic Acid - chemistry</topic><topic>Hyaluronic Acid - metabolism</topic><topic>Hyaluronoglucosaminidase - chemistry</topic><topic>Hyaluronoglucosaminidase - metabolism</topic><topic>Light</topic><topic>Lipase - chemistry</topic><topic>Lipase - metabolism</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred ICR</topic><topic>Microscopy, Electron, Transmission</topic><topic>Multicellular spheroids</topic><topic>Nanogel hyaluronic acid</topic><topic>Nanomedicine</topic><topic>Nanoparticles</topic><topic>NIH 3T3 Cells</topic><topic>Particle Size</topic><topic>Scattering, Radiation</topic><topic>Solubility</topic><topic>Spectroscopy, Fourier Transform Infrared</topic><topic>Spheroids, Cellular</topic><topic>Surface Properties</topic><topic>Technology, Pharmaceutical - methods</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Chenchen</creatorcontrib><creatorcontrib>Wang, Xin</creatorcontrib><creatorcontrib>Yao, Xikuang</creatorcontrib><creatorcontrib>Zhang, Yajun</creatorcontrib><creatorcontrib>Wu, Wei</creatorcontrib><creatorcontrib>Jiang, Xiqun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of controlled release</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yang, Chenchen</au><au>Wang, Xin</au><au>Yao, Xikuang</au><au>Zhang, Yajun</au><au>Wu, Wei</au><au>Jiang, Xiqun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hyaluronic acid nanogels with enzyme-sensitive cross-linking group for drug delivery</atitle><jtitle>Journal of controlled release</jtitle><addtitle>J Control Release</addtitle><date>2015-05-10</date><risdate>2015</risdate><volume>205</volume><spage>206</spage><epage>217</epage><pages>206-217</pages><issn>0168-3659</issn><eissn>1873-4995</eissn><abstract>A methacrylation strategy was employed to functionalize hyaluronic acid and prepare hyaluronic acid (HA) nanogels. Dynamic light scattering, zeta potential analyzer and electron microscopy were utilized to characterize the nanogels and their enzyme-degradability in vitro. It was found that these nanogels had a spherical morphology with the diameter of about 70nm, and negative surface potential. When doxorubicin (DOX) was loaded into the nanogels, the diameter decreased to approximately 50nm with a drug loading content of 16% and encapsulation efficiency of 62%. Cellular uptake examinations showed that HA nanogels could be preferentially internalized by two-dimensional (2D) cells and three-dimensional (3D) multicellular spheroids (MCs) which both overexpress CD44 receptor. Near-infrared fluorescence imaging, biodistribution and penetration examinations in tumor tissue indicated that the HA nanogels could efficiently accumulate and penetrate the tumor matrix. In vivo antitumor evaluation found that DOX-loaded HA nanogels exhibited a significantly superior antitumor effect. Doxorubicin-loaded hyaluronic acid nanogels were synthesized by a methacrylated strategy. In vitro cellular uptake shows that these nanogels were preferentially internalized by the CD44 or CD168-overexpressed cancer cells. In vivo antitumor examination indicates that these nanogels suppress tumor growth distinctly. [Display omitted]</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>25665867</pmid><doi>10.1016/j.jconrel.2015.02.008</doi><tpages>12</tpages></addata></record>
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subjects Animals
Antibiotics, Antineoplastic - chemistry
Antibiotics, Antineoplastic - metabolism
Antibiotics, Antineoplastic - pharmacology
Cell Survival - drug effects
Chemistry, Pharmaceutical
Dose-Response Relationship, Drug
Doxorubicin - chemistry
Doxorubicin - metabolism
Doxorubicin - pharmacology
Drug Carriers
Drug delivery
Gels
Hep G2 Cells
Humans
Hyaluronan Receptors - metabolism
Hyaluronic Acid - analogs & derivatives
Hyaluronic Acid - chemistry
Hyaluronic Acid - metabolism
Hyaluronoglucosaminidase - chemistry
Hyaluronoglucosaminidase - metabolism
Light
Lipase - chemistry
Lipase - metabolism
Male
Mice
Mice, Inbred ICR
Microscopy, Electron, Transmission
Multicellular spheroids
Nanogel hyaluronic acid
Nanomedicine
Nanoparticles
NIH 3T3 Cells
Particle Size
Scattering, Radiation
Solubility
Spectroscopy, Fourier Transform Infrared
Spheroids, Cellular
Surface Properties
Technology, Pharmaceutical - methods
Time Factors
title Hyaluronic acid nanogels with enzyme-sensitive cross-linking group for drug delivery
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