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Hyaluronic acid conjugated nanoparticle delivery of siRNA against TWIST reduces tumor burden and enhances sensitivity to cisplatin in ovarian cancer.
Shahin, Sophia A; Wang, Ruining; Simargi, Shirleen I; Contreras, Altagracia; Parra Echavarria, Liliana; Qu, Louise; Wen, Wei; Dellinger, Thanh; Unternaehrer, Juli; Tamanoi, Fuyuhiko; Zink, Jeffrey I; Glackin, Carlotta A.
Afiliação
  • Shahin SA; Irell & Manella Graduate School of Biological Sciences, City of Hope - Beckman Research Institute, Duarte, California, USA; Department of Stem Cell and Developmental Biology, City of Hope - Beckman Research Institute, Duarte, California, USA.
  • Wang R; Department of Chemistry and Biochemistry, California NanoSystems Institute, University of California Los Angeles, Los Angeles, California, USA.
  • Simargi SI; Department of Stem Cell and Developmental Biology, City of Hope - Beckman Research Institute, Duarte, California, USA; Department of Biological Sciences, California State University, Pomona, CA.
  • Contreras A; Department of Stem Cell and Developmental Biology, City of Hope - Beckman Research Institute, Duarte, California, USA; Department of Biological Sciences, California State University, Long Beach, CA.
  • Parra Echavarria L; Department of Stem Cell and Developmental Biology, City of Hope - Beckman Research Institute, Duarte, California, USA.
  • Qu L; Irell & Manella Graduate School of Biological Sciences, City of Hope - Beckman Research Institute, Duarte, California, USA; Department of Stem Cell and Developmental Biology, City of Hope - Beckman Research Institute, Duarte, California, USA.
  • Wen W; Department of Surgery, City of Hope - Beckman Research Institute, Duarte, California, USA.
  • Dellinger T; Department of Surgery, City of Hope - Beckman Research Institute, Duarte, California, USA.
  • Unternaehrer J; Department of Biochemistry, Loma Linda University School of Medicine, Loma Linda, CA.
  • Tamanoi F; Department of Microbiology, Immunology, and Molecular Genetics, Jonsson Comprehensive Cancer Center, California NanoSystems Institute, University of California Los Angeles, Los Angeles, California, USA.
  • Zink JI; Department of Chemistry and Biochemistry, California NanoSystems Institute, University of California Los Angeles, Los Angeles, California, USA.
  • Glackin CA; Irell & Manella Graduate School of Biological Sciences, City of Hope - Beckman Research Institute, Duarte, California, USA; Department of Stem Cell and Developmental Biology, City of Hope - Beckman Research Institute, Duarte, California, USA. Electronic address: cglackin@coh.org.
Nanomedicine ; 14(4): 1381-1394, 2018 06.
Article em En | MEDLINE | ID: mdl-29665439
ABSTRACT
TWIST protein is critical to development and is activated in many cancers. TWIST regulates epithelial-mesenchymal transition, and is linked to angiogenesis, metastasis, cancer stem cell phenotype, and drug resistance. The majority of epithelial ovarian cancer (EOC) patients with metastatic disease respond well to first-line chemotherapy but most relapse with disease that is both metastatic and drug resistant, leading to a five-year survival rate under 20%. We are investigating the role of TWIST in mediating these relapses. We demonstrate TWIST-siRNA (siTWIST) and a novel nanoparticle delivery platform to reverse chemoresistance in an EOC model. Hyaluronic-acid conjugated mesoporous silica nanoparticles (MSN-HAs) carried siTWIST into target cells and led to sustained TWIST knockdown in vitro. Mice treated with siTWIST-MSN-HA and cisplatin exhibited specific tumor targeting and reduction of tumor burden. This platform has potential application for overcoming clinical challenges of tumor cell targeting, metastasis and chemoresistance in ovarian and other TWIST overexpressing cancers.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Cisplatino / RNA Interferente Pequeno / Nanopartículas / Ácido Hialurônico Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Animals / Female / Humans Idioma: En Revista: Nanomedicine Assunto da revista: BIOTECNOLOGIA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Cisplatino / RNA Interferente Pequeno / Nanopartículas / Ácido Hialurônico Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Animals / Female / Humans Idioma: En Revista: Nanomedicine Assunto da revista: BIOTECNOLOGIA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos