dc.contributor.author |
Feng, Shuaishuai |
en |
dc.contributor.author |
Wu, Zi-Xin |
en |
dc.contributor.author |
Zhao, Ziyan |
en |
dc.contributor.author |
Liu, Jinhu |
en |
dc.contributor.author |
Sun, Kaoxiang |
en |
dc.contributor.author |
Guo, Chuanyou |
en |
dc.contributor.author |
Wang, Hongbo |
en |
dc.contributor.author |
Wu, Zimei |
en |
dc.date.accessioned |
2019-06-19T02:12:31Z |
en |
dc.date.issued |
2019-02-07 |
en |
dc.identifier.issn |
1944-8244 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/47199 |
en |
dc.description.abstract |
This study aimed to develop an efficient step-by-step osteosarcoma (OS)-targeting liposome system functionalized with a redox-cleavable, bone- and cluster of differentiation 44 (CD44)-dual-targeting polymer. Furthermore, the effect of coadministration of a tumor-penetrating peptide, internalizing RGD (iRGD), was investigated. First, a bone-targeting moiety, alendronate (ALN), was conjugated with hyaluronic acid (HA), a ligand for CD44. This ALN-HA conjugate was coupled with DSPE-PEG2000-COOH through a bioreducible disulfide linker (-SS-) to obtain a functionalized lipid, ALN-HA-SS-L, to be postinserted into preformed liposomes loaded with doxorubicin (DOX). The roles of ALN, HA, and the redox sensitivity of the ALN-HA-SS-L liposomes (ALN-HA-SS-L-L) in the anti-OS effect were critically evaluated against various reference liposomal formulations (with only ALN, HA, or redox sensitivity). ALN-HA-SS-L-L displayed a zeta potential of -26.07 ± 0.32 mV and selectively disassembled in the presence of a reducing agent, 10 mM glutathione, which can be found in cancer cells. Compared to various reference liposomes, ALN-HA-SS-L-L/DOX had significantly higher cytotoxicity to human OS MG-63 cells alongside high and rapid cellular uptake. In the orthotopic OS nude mouse models, ALN-HA-SS-L-L/DOX showed remarkable tumor growth suppression and prolonged survival time. This result was further improved by the coadministration of iRGD. The antitumor effects of various liposomes were ranked in the same order as the degree of tumor biodistribution shown by in vivo/ex vivo imaging: ALN-HA-SS-L-L coadministered with iRGD > ALN-HA-SS-L-L > HA-SS-L-L > HA-L-L > PEG-L> free drug. ALN-HA-SS-L-L/DOX also reduced the cardiotoxicity of DOX and lung metastases. Overall, this study demonstrated that ALN-HA-SS-L-L/DOX, equipped with bone- and CD44-dual-targeting abilities and redox sensitivity, could be a promising OS-targeted therapy. The efficacy could also be augmented by coadministration of iRGD. |
en |
dc.format.medium |
Print-Electronic |
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dc.language |
eng |
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dc.relation.ispartofseries |
ACS applied materials & interfaces |
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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 |
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dc.subject |
Cell Line, Tumor |
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dc.subject |
Animals |
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dc.subject |
Mice, Inbred BALB C |
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dc.subject |
Humans |
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dc.subject |
Mice, Nude |
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dc.subject |
Osteosarcoma |
en |
dc.subject |
Bone Neoplasms |
en |
dc.subject |
Alendronate |
en |
dc.subject |
Neoplasm Proteins |
en |
dc.subject |
Liposomes |
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dc.subject |
Xenograft Model Antitumor Assays |
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dc.subject |
Cell Survival |
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dc.subject |
Female |
en |
dc.subject |
Hyaluronan Receptors |
en |
dc.title |
Engineering of Bone- and CD44-Dual-Targeting Redox-Sensitive Liposomes for the Treatment of Orthotopic Osteosarcoma. |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1021/acsami.8b18820 |
en |
pubs.issue |
7 |
en |
pubs.begin-page |
7357 |
en |
pubs.volume |
11 |
en |
dc.rights.holder |
Copyright: The author |
en |
pubs.end-page |
7368 |
en |
pubs.publication-status |
Published |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Journal Article |
en |
pubs.elements-id |
763127 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
Pharmacy |
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dc.identifier.eissn |
1944-8252 |
en |
pubs.record-created-at-source-date |
2019-01-26 |
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pubs.dimensions-id |
30682240 |
en |