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SMO-CRISPR-mediated apoptosis in CD133-targeted cancer stem cells and tumor growth inhibition

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dc.contributor.authorPandey, S-
dc.contributor.authorLee, M-
dc.contributor.authorLim, J-
dc.contributor.authorPark, S-
dc.contributor.authorChoung, YH-
dc.contributor.authorKim, JE-
dc.contributor.authorGarg, P-
dc.contributor.authorChung, JH-
dc.date.accessioned2023-05-23T04:04:31Z-
dc.date.available2023-05-23T04:04:31Z-
dc.date.issued2023-
dc.identifier.issn0168-3659-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/25592-
dc.description.abstractCancer stem cells (CSCs) possess the ability to indefinitely proliferate and resist therapy, leading to cancer relapse and metastasis. To address this, we aimed to develop a CSC-inclusive therapy that targets both CSCs and non-CSC glioblastoma (GBM) cells. We accomplished this by using a smoothened (SMO) CRISPR/Cas9 plasmid to suppress the hedgehog pathway in CSCs, in combination with inhibiting the serine hydroxymethyl transferase 1 (SHMT1)-driven thymidylate biosynthesis pathway in non-CSC GBM cells using SHMT1 siRNA (siSHMT1). We targeted CSCs using a CD133 peptide attached to an osmotically active vitamin B6-coupled polydixylitol vector (VPX-CD133) by a photoactivatable heterobifunctional linker. VPX-CD133 nanocomplexes in comparison to VPX complexes remarkably targeted and transfected CSCs both in vitro and in subcutaneous tumor. The VPX-CD133-mediated targeted delivery of SMO CRISPR in CSCs led to SMO suppression that negatively affected its growth. Next, we performed comprehensive therapy in xenograft mice using VPX-CD133, which delivered SMO-CRISPR to CSCs, and VPX, which delivered siSHMT1 to non-CSC GBM cells. The combined treatment induced apoptosis in a large number of cells, reduced tumor volume by up to 81%, and improved the health of treated mice significantly. By eliminating CSCs together with the non-CSC GBM cells, the combined study paves the way for developing CSC-inclusive therapies for GBM.-
dc.language.isoen-
dc.subject.MESHAC133 Antigen-
dc.subject.MESHAnimals-
dc.subject.MESHApoptosis-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHGlioblastoma-
dc.subject.MESHHedgehog Proteins-
dc.subject.MESHHumans-
dc.subject.MESHMice-
dc.subject.MESHNeoplastic Stem Cells-
dc.subject.MESHRNA, Small Interfering-
dc.subject.MESHSmoothened Receptor-
dc.titleSMO-CRISPR-mediated apoptosis in CD133-targeted cancer stem cells and tumor growth inhibition-
dc.typeArticle-
dc.identifier.pmid36931470-
dc.subject.keywordCancer stem cells-
dc.subject.keywordCD133-
dc.subject.keywordCRISPR-
dc.subject.keywordGlioblastoma-
dc.subject.keywordSHMT1-
dc.subject.keywordSmoothened-
dc.contributor.affiliatedAuthorChoung, YH-
dc.type.localJournal Papers-
dc.identifier.doi10.1016/j.jconrel.2023.03.023-
dc.citation.titleJournal of controlled release-
dc.citation.volume357-
dc.citation.date2023-
dc.citation.startPage94-
dc.citation.endPage108-
dc.identifier.bibliographicCitationJournal of controlled release, 357. : 94-108, 2023-
dc.embargo.liftdate9999-12-31-
dc.embargo.terms9999-12-31-
dc.identifier.eissn1873-4995-
dc.relation.journalidJ001683659-
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Journal Papers > School of Medicine / Graduate School of Medicine > Otolaryngology
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