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dc.contributor.authorHuang, Wei-Tingen_US
dc.contributor.authorLarsson, Mikaelen_US
dc.contributor.authorLee, Yi-Chien_US
dc.contributor.authorLiu, Dean-Moen_US
dc.contributor.authorChiou, Guang-Yuhen_US
dc.date.accessioned2017-04-21T06:55:24Z-
dc.date.available2017-04-21T06:55:24Z-
dc.date.issued2016-12en_US
dc.identifier.issn0939-6411en_US
dc.identifier.urihttp://dx.doi.org/10.1016/j.ejpb.2016.10.014en_US
dc.identifier.urihttp://hdl.handle.net/11536/132994-
dc.description.abstractLung cancer kills more humans than any other cancer and multidrug resistance (MDR) in cancer stem like cells (CSC) is emerging as a reason for failed treatments. One concept that addresses this root cause of treatment failure is the utilization of nanoparticles to simultaneously deliver dual drugs to cancer cells with synergistic performance, easy to envision - hard to achieve. (1) It is challenging to simultaneously load drugs of highly different physicochemical properties into one nanoparticle, (2) release kinetics may differ between drugs and (3) general requirements for biomedical nanoparticles apply. Here self-assembled nanoparticles of amphiphilic carboxymethyl-hexanoyl chitosan (CHC) were shown to present nano-microenvironments enabling simultaneous loading of hydrophilic and hydrophobic drugs. This was expanded into a dual-drug nano-delivery system to treat lung CSC. CHC nanoparticles were loaded/chemically modified with the anticancer drug cisplatin and the MDR-suppressing Chinese herbal extract demethoxycurcumin, followed by biofunctionalization with CD133 antibody for enhanced uptake by lung CSC, all in a feasible one-pot preparation. The nanoparticles were characterized with regard to chemistry, size, zeta potential and drug loading/release. Biofunctionalized and non-functionalized nanoparticles were investigated for uptake by lung CSC. Subsequently the cytotoxicity of single and dual drugs, free in solution or in nanoparticles, was evaluated against lung CSC at different doses. From the dose response at different concentrations the degree of synergy was determined through Chou-Talalay\'s Plot. The bio-functionalized nanoparticles promoted synergistic effects between the drugs and were highly effective against MDR lung CSC. The efficacy and feasible one-pot preparation suggests preclinical studies using relevant disease models to be justified. (C) 2016 Elsevier B.V. All rights reserved.en_US
dc.language.isoen_USen_US
dc.subjectBiodegradable chitosan nanoparticleen_US
dc.subjectCD133en_US
dc.subjectCDDPen_US
dc.subjectDual-drug deliveryen_US
dc.subjectSynergistic effecten_US
dc.titleDual drug-loaded biofunctionalized amphiphilic chitosan nanoparticles: Enhanced synergy between cisplatin and demethoxycurcumin against multidrug-resistant stem-like lung cancer cellsen_US
dc.identifier.doi10.1016/j.ejpb.2016.10.014en_US
dc.identifier.journalEUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICSen_US
dc.citation.volume109en_US
dc.citation.spage165en_US
dc.citation.epage173en_US
dc.contributor.department材料科學與工程學系zh_TW
dc.contributor.department生物科技學院zh_TW
dc.contributor.department生物科技學系zh_TW
dc.contributor.departmentDepartment of Materials Science and Engineeringen_US
dc.contributor.departmentCollege of Biological Science and Technologyen_US
dc.contributor.departmentDepartment of Biological Science and Technologyen_US
dc.identifier.wosnumberWOS:000390496500018en_US
Appears in Collections:Articles