Estrogen-functionalized liposomes grafted with glutathione-responsive sheddable chotooligosaccharides for the therapy of osteosarcoma.

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dc.contributor.author Yin, Xuelei en
dc.contributor.author Feng, Shuaishuai en
dc.contributor.author Chi, Yingying en
dc.contributor.author Liu, Jinhu en
dc.contributor.author Sun, Kaoxiang en
dc.contributor.author Guo, Chuanyou en
dc.contributor.author Wu, Zimei en
dc.date.accessioned 2019-03-20T03:56:57Z en
dc.date.issued 2018-11 en
dc.identifier.citation Drug delivery 25(1):900-908 Nov 2018 en
dc.identifier.issn 1071-7544 en
dc.identifier.uri http://hdl.handle.net/2292/46172 en
dc.description.abstract An estrogen (ES)-functionalized cationic liposomal system was developed and exploited for targeted delivery to osteosarcoma. Natural biocompatible chotooligosaccharides (COS, MW2-5 KDa) were covalently tethered to the liposomal surface through a disulfate bond (-SS-) to confer reduction-responsive COS detachment, whereas estrogen was grafted via polyethylene glycol (PEG 2 K) chain to achieve estrogen receptor-targeting. The liposomal carriers were prepared by the ethanol injection method and fluorescent anticancer drug doxorubicin (DOX) was loaded with ammonium sulfate gradient. The physicochemical properties, reduction-sensitivity, and the roles of estrogen on cellular uptake and tumor-targeting were studied. The Chol-SS-COS/ES/DOX liposomes were spherical with an average size about 110 nm, and high encapsulation efficiency. The liposomes were stable in physiological condition but rapidly release the payload in response to tumoral intracellular glutathione (20 mM). MTT cytotoxicity assay confirmed that Chol-SS-COS/ES/DOX liposomes exhibited higher cytotoxicity to MG63 osteosarcoma cells than to liver cells (LO2). Flow cytometry (FCM) and confocal laser scanning microscopy revealed that cellular uptake of Chol-SS-COS/ES/DOX liposomes by MG63, than the free DOX or Chol-SS-COS/DOX. Ex vivo fluorescence distribution study showed that the multifunctional liposomes selectively accumulated in the MG63 xenografts versus the organs. Chol-SS-COS/ES/DOX liposomes strongly inhibited the tumor growth and enhanced the animal survival rate. Overall, the COS grafted estrogen-functionalized cationic liposomes, fortified with glutathione-responsiveness, showed great potential for specific intracellular drug delivery to estrogen receptor-expressing tumors such as osteosarcoma. en
dc.format.medium Print en
dc.language eng en
dc.relation.ispartofseries Drug delivery en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.rights.uri http://creativecommons.org/licenses/by/4.0/ en
dc.subject Cell Line, Tumor en
dc.subject Animals en
dc.subject Mice, Inbred BALB C en
dc.subject Humans en
dc.subject Mice, Nude en
dc.subject Osteosarcoma en
dc.subject Bone Neoplasms en
dc.subject Polyethylene Glycols en
dc.subject Doxorubicin en
dc.subject Cholesterol en
dc.subject Estrone en
dc.subject Chitin en
dc.subject Glutathione en
dc.subject Receptors, Estrogen en
dc.subject Antibiotics, Antineoplastic en
dc.subject Liposomes en
dc.subject Tumor Burden en
dc.subject Injections, Intravenous en
dc.subject Xenograft Model Antitumor Assays en
dc.subject Technology, Pharmaceutical en
dc.subject Drug Compounding en
dc.subject Tissue Distribution en
dc.subject Particle Size en
dc.subject Time Factors en
dc.subject Male en
dc.subject Drug Liberation en
dc.title Estrogen-functionalized liposomes grafted with glutathione-responsive sheddable chotooligosaccharides for the therapy of osteosarcoma. en
dc.type Journal Article en
dc.identifier.doi 10.1080/10717544.2018.1458920 en
pubs.issue 1 en
pubs.begin-page 900 en
pubs.volume 25 en
dc.rights.holder Copyright: The authors en
dc.identifier.pmid 29644882 en
pubs.end-page 908 en
pubs.publication-status Published en
dc.rights.accessrights http://purl.org/eprint/accessRights/OpenAccess en
pubs.subtype research-article en
pubs.subtype Journal Article en
pubs.elements-id 736109 en
pubs.org-id Medical and Health Sciences en
pubs.org-id Pharmacy en
dc.identifier.eissn 1521-0464 en
pubs.record-created-at-source-date 2018-04-13 en
pubs.dimensions-id 29644882 en


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