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Nanovesicle-mediated systemic delivery of microRNA-34a for CD44 overexpressing gastric cancer stem cell therapy

DC Field Value Language
dc.contributor.author서진석-
dc.contributor.author손혜영-
dc.contributor.author허용민-
dc.date.accessioned2017-10-26T07:21:26Z-
dc.date.available2017-10-26T07:21:26Z-
dc.date.issued2016-
dc.identifier.issn0142-9612-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/151922-
dc.description.abstractThe cancer stem cell (CSC) hypothesis postulates that cancer cells overexpressing CD44 are marked as CSCs that cause tumorigenesis and recurrence. This hypothesis suggests that CD44 is a potential therapeutic target that can interfere with CSCs qualities. MicroRNA-34a (miR-34a) is a promising candidate for CD44 repression-based cancer therapy as it has been reported to inhibit proliferation, metastasis, and survival of CD44-positive CSCs. Here, we used nanovesicles containing PLI/miR complexes (NVs/miR) to systemically deliver miR-34a and induce miR-34a-triggered CD44 suppression in orthotopically and subcutaneously implanted tumors in nude mice. Poly(l-lysine-graft-imidazole) (PLI) condenses miRs and is functionally modified to deliver miRs to the site of action by buffering effect of imidazole residues under endosomal pH. Indeed, NVs/miR consisting of PEGylated lipids enveloping PLI/miR complexes greatly reduced inevitable toxicity of polycations by compensating their surface charge and markedly improved their in vivo stability and accumulation to tumor tissue compared to PLI/miR polyplexes. Our NVs-mediated miR-34a delivery system specifically increased endogenous target miR levels, thereby attenuating proliferation and migration of gastric cancer cells by repressing the expression of CD44 with decreased levels of Bcl-2, Oct 3/4 and Nanog genes. Our strategy led to a greater therapeutic outcome than PLI-based delivery with highly selective tumor cell death and significantly delayed tumor growth in CD44-positive tumor-bearing mouse models, thus providing a fundamental therapeutic window for CSCs.-
dc.description.statementOfResponsibilityrestriction-
dc.publisherElsevier Science-
dc.relation.isPartOfBIOMATERIALS-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAnimals-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHHumans-
dc.subject.MESHHyaluronan Receptors/metabolism*-
dc.subject.MESHMale-
dc.subject.MESHMice-
dc.subject.MESHMice, Inbred BALB C-
dc.subject.MESHMicroRNAs/administration & dosage*-
dc.subject.MESHMolecular Targeted Therapy/methods-
dc.subject.MESHNanocapsules/administration & dosage*-
dc.subject.MESHNanocapsules/chemistry-
dc.subject.MESHNanoconjugates/administration & dosage-
dc.subject.MESHNanoconjugates/chemistry-
dc.subject.MESHNeoplastic Stem Cells/drug effects*-
dc.subject.MESHNeoplastic Stem Cells/metabolism*-
dc.subject.MESHNeoplastic Stem Cells/pathology-
dc.subject.MESHStomach Neoplasms/metabolism*-
dc.subject.MESHStomach Neoplasms/therapy*-
dc.subject.MESHTreatment Outcome-
dc.titleNanovesicle-mediated systemic delivery of microRNA-34a for CD44 overexpressing gastric cancer stem cell therapy-
dc.typeArticle-
dc.publisher.locationNetherlands-
dc.contributor.collegeCollege of Medicine-
dc.contributor.departmentDept. of Radiology-
dc.contributor.googleauthorEunji Jang-
dc.contributor.googleauthorEunjung Kim-
dc.contributor.googleauthorHye-Young Son-
dc.contributor.googleauthorEun-Kyung Lim-
dc.contributor.googleauthorHwunjae Lee-
dc.contributor.googleauthorYuna Choi-
dc.contributor.googleauthorKwangyeol Park-
dc.contributor.googleauthorSeungmin Han-
dc.contributor.googleauthorJin-Suck Suh-
dc.contributor.googleauthor, Yong-Min Huh-
dc.contributor.googleauthorSeungjoo Haam-
dc.identifier.doi10.1016/j.biomaterials.2016.07.036-
dc.contributor.localIdA04589-
dc.contributor.localIdA04359-
dc.contributor.localIdA01916-
dc.relation.journalcodeJ00312-
dc.identifier.eissn1878-5905-
dc.identifier.pmid27497057-
dc.identifier.urlhttp://www.sciencedirect.com/science/article/pii/S0142961216303738?via%3Dihub-
dc.subject.keywordCD44 suppression-
dc.subject.keywordCancer stem cells-
dc.subject.keywordNanovesicles-
dc.subject.keywordmiR-34a delivery-
dc.subject.keywordpH-responsive-
dc.contributor.alternativeNameSuh, Jin Suck-
dc.contributor.alternativeNameSon, Hye Yeong-
dc.contributor.alternativeNameHuh, Yong Min-
dc.contributor.affiliatedAuthorSon, Hye Yeong-
dc.contributor.affiliatedAuthorHuh, Yong Min-
dc.contributor.affiliatedAuthorSuh, Jin Suck-
dc.citation.volume105-
dc.citation.startPage12-
dc.citation.endPage24-
dc.identifier.bibliographicCitationBIOMATERIALS, Vol.105 : 12-24, 2016-
dc.date.modified2017-10-24-
dc.identifier.rimsid46247-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers

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