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This study introduces a targeted carrier that delivers an inducible caspase-9 suicide gene (pLVSIN-iC9) using graphene oxide quantum dots decorated with polyethyleneimine and the MUC1-binding aptamer S2.2. Overexpression of MUC1 enables selective targeting of luminal breast cancer cells. A coculture organoid model is generated and characterized, and targeted therapy demonstrates an organoid-specific killing effect by iC9, supporting strong potential for selective gene delivery.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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gene therapy approach does the study target?","Question",{"text":63,"@type":64},"The study focuses on suicide gene therapy delivering an inducible caspase-9 suicide gene (pLVSIN-iC9), which triggers apoptosis upon activation.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How does the carrier achieve selective targeting of breast cancer cells?",{"text":68,"@type":64},"The carrier uses graphene oxide quantum dots decorated with polyethyleneimine and the MUC1-binding aptamer S2.2, enabling selective binding to MUC1-overexpressing cancer cells.",{"name":70,"@type":61,"acceptedAnswer":71},"Why was an organoid coculture model used in this research?",{"text":72,"@type":64},"An organoid model better mimics solid tumor tissue structure and microenvironment, allowing evaluation of the targeted therapeutic effect in a more tissue-relevant 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nature.com/scientificreports)  \nOPEN  \nAptamer-guided graphene oxide quantum dots for targeted suicide gene therapy in an organoid model of luminal breast cancer  \nReza Taghizadeh-Tabarsi1, Shiva Akbari-Birgani1,2􀀍, MehrnazAmjadi1, Soheila Mohammadi3, Nasser Nikfarjam4,5 & Kosuke Kusamori6  \nBreast cancer is one of the most common cancers in women. One of the best therapeutic methods against breast cancer is gene therapy, while having an appropriate gene carrier is the biggest challenge of gene therapy. Hence, developing carriers with low cytotoxicity and high gene transfection efficiency, and preferentially with the selective function of gene delivery is a critical demand for this method. In the present study, we introduce a novel targeted carrier to deliver the inducible caspase-9 suicide gene (pLVSIN-iC9) into breast cancer cells. The carrier is composed of graphene oxide quantum dots decorated with polyethyleneimine, and S2.2; an aptamer with high affinity to MUC1 (GOQD-PEI/S2.2) . Duetothe overexpression of MUC1 in breast cancer cells, the designed GOQD-PEI/S2.2/pLVSIN-iC9 can selectively target cancer cells. Moreover, to better mimic solid tumor conditions, and to evaluate the selective effect of the GOQD-PEI/S2.2/pLVSIN-iC9, an organoid model derived from human dermal fibroblasts (HDF) and MCF-7 cells (coculture organoid) was generated and characterized. The results demonstrate that the coculture organoid model adapts the tissue structure of luminal breast cancer, as well. Therefore, the organoids were subjected to treatment with targeted gene therapy using GOQDPEI/S2.2/pLVSIN-iC9. Our evidence supports the targeted killing effect of iC9 on the breast cancer cells of the organoids and suggests the good potential of the newly introduced carriers in targeted gene delivery.  \nKeywords Suicide gene therapy, Graphen oxide quantum dot (GOQD), Luminal breast cancer, Organoid model, Gene delivery  \nAbbreviations  \nGOQD Graphene oxide quantum dots PEI Polyethylene imine  \niC9 inducible Caspase 9  \nDLS Dynamic light scattering SEM Scanning electron microscope  \nCancer stands as the second leading global cause of mortality among diseases1. Among women, breast cancer prevails as the most frequent form of cancer. Tailoring treatment for breast cancer hinges on subtype, stage, and grade. Conventional breast cancer treatments encompass chemotherapy, radiotherapy, and endocrine therapy. Nonetheless, these approaches encounter challenges like treatment resistance. Consequently, it is crucial to identify treatment strategies with fewer impediments. One potential approach with reduced challenges is suicide gene therapy. inducible caspase 9 (iC9) is one of the suicide genes explored in breast cancer treatment is2,3.  \n1Department of Biological Sciences, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan 4513766731, Iran. 2Research Center for Basic Sciences and Modern Technologies (RBST), Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan, Iran. 3Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran. 4Department of Chemical Engineering, College of Engineering and Computing, University of South Carolina, Columbia, SC 29208, USA. 5Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan 4513766731, Iran. 6Laboratory of Cellular Drug Discovery and Development, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan. 􀀍 email: [sh.akbari@iasbs.ac.ir](sh.akbari@iasbs.ac.ir)  \n[www. nature.com/scientificreports/](www. nature.com/scientificreports/)  \niC9 closely resembles caspase 9, a member of the caspase family, triggering apoptosis, albeit with a distinction: it features an FKBP12 domain rather than a CARD domain. Upon exposure to chemical inducers (such as AP1903), the two FKBP12 domains dimerize, triggering the dimerization of iC9 . This dimerization proces","cbCailMFg5KuLBpX","https://ap.wps.com/l/cbCailMFg5KuLBpX","pdf",2333583,13,"English","# Abstract\n# Introduction and Rationale\n## Gene therapy and the need for suitable carriers\n## Suicide gene therapy and iC9 activation\n# Targeted Carrier Design\n## GOQD-PEI and aptamer S2.2 targeting\n## MUC1 overexpression and selectivity\n# Organoid Model Development\n## Coculture organoid generation and characterization","[{\"question\":\"What gene therapy approach does the study target?\",\"answer\":\"The study focuses on suicide gene therapy delivering an inducible caspase-9 suicide gene (pLVSIN-iC9), which triggers apoptosis upon activation.\"},{\"question\":\"How does the carrier achieve selective targeting of breast cancer cells?\",\"answer\":\"The carrier uses graphene oxide quantum dots decorated with polyethyleneimine and the MUC1-binding aptamer S2.2, enabling selective binding to MUC1-overexpressing cancer cells.\"},{\"question\":\"Why was an organoid coculture model used in this research?\",\"answer\":\"An organoid model better mimics solid tumor tissue structure and microenvironment, allowing evaluation of the targeted therapeutic effect in a more tissue-relevant system.\"}]","Aptamer-guided graphene oxide quantum dots for targeted suicide gene therapy in an organoid model of luminal breast cancer | PDF",1789998927,33]