A shell-crosslinked polymeric micelle system for pH/redox dual stimuli-triggered DOX on-demand release and enhanced antitumor activity.

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dc.contributor.author Wang, Lele en
dc.contributor.author Zhang, Jing en
dc.contributor.author Song, Meijia en
dc.contributor.author Tian, Baocheng en
dc.contributor.author Li, Keke en
dc.contributor.author Liang, Yan en
dc.contributor.author Han, Jingtian en
dc.contributor.author Wu, Zimei en
dc.date.accessioned 2019-03-20T04:00:19Z en
dc.date.issued 2017-04 en
dc.identifier.issn 0927-7765 en
dc.identifier.uri http://hdl.handle.net/2292/46181 en
dc.description.abstract Based on targeted amphiphilic block copolymer N-acetyl glucosamine-poly (styrene-alt-maleic anhydride)58-b-polystyrene130 (NAG-P(St-alt-MA)58-b-PSt130), a pH/redox dual-triggered shell-crosslinked polymeric micelle system was constructed. The shell-crosslinked micelles (CLM) were prepared by post-crosslinking method to regulate drug release kinetics using cystamine as linkers between carboxy groups of the shell. Compared with non-crosslinked micelles (NCLM), CLM showed spherical shapes with little increased mean diameter of 102.40±0.54nm, low polydispersity index (PDI) of 0.19±0.36, enlarged zeta potential value from -41.46±0.99 to -9.31±0.50mV, indicating the successful modification of disulfide bonds in shell. In vitro drug release study clearly exhibited a pH and redox dual-sensitive drug release profile with significantly accelerated drug release under pH 5.0 and 10mM GSH conditions (46.84% in 96h) without burst release. Both CLM and NCLM showed quite different release profiles between physiological (pH 7.4) and tumoral microenvironment (pH 5.0), effectively avoiding the premature drug leakage and realizing on-demand drug release. The MTT assay implied that CLM presented a time- and concentration-dependent manner to inhibit proliferation of A549 and MCF-7 cells and much lower IC50 values in comparison with that of NCLM after 72h incubation. Both FCM and CLSM results showed that CLM displayed much higher cellular uptake efficiency and anti-tumor activities than NCLM and free DOX. CLM and NCLM could be internalized by energy-dependent endocytosis mechanism due to similar surface properties. Overall, this dual-stimuli triggered micelle system provided a promising tumor-responsive platform for cancer therapy. en
dc.format.medium Print-Electronic en
dc.language eng en
dc.relation.ispartofseries Colloids and surfaces. B, Biointerfaces 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.subject Humans en
dc.subject Doxorubicin en
dc.subject Polymers en
dc.subject Antibiotics, Antineoplastic en
dc.subject Drug Carriers en
dc.subject Inhibitory Concentration 50 en
dc.subject Cell Proliferation en
dc.subject Micelles en
dc.subject Hydrogen-Ion Concentration en
dc.subject MCF-7 Cells en
dc.subject A549 Cells en
dc.title A shell-crosslinked polymeric micelle system for pH/redox dual stimuli-triggered DOX on-demand release and enhanced antitumor activity. en
dc.type Journal Article en
dc.identifier.doi 10.1016/j.colsurfb.2016.12.032 en
pubs.begin-page 1 en
pubs.volume 152 en
dc.rights.holder Copyright: The author en
dc.identifier.pmid 28063272 en
pubs.end-page 11 en
pubs.publication-status Published en
dc.rights.accessrights http://purl.org/eprint/accessRights/RestrictedAccess en
pubs.subtype Journal Article en
pubs.elements-id 609168 en
pubs.org-id Medical and Health Sciences en
pubs.org-id Pharmacy en
dc.identifier.eissn 1873-4367 en
pubs.record-created-at-source-date 2017-01-07 en
pubs.dimensions-id 28063272 en

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