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Inhibition of NADPH Oxidase-ROS Signal using Hyaluronic Acid Nanoparticles for Overcoming Radioresistance in Cancer Therapy.
Zhu, Lei; Zhao, Yi; Liu, Tongrui; Chen, Minglong; Qian, Wei Ping; Jiang, Binghua; Barwick, Benjamin G; Zhang, Lumeng; Styblo, Toncred M; Li, Xiaoxian; Yang, Lily.
Afiliación
  • Zhu L; Department of Surgery and Winship Cancer Institute, Emory University School of Medicine, Atlanta 30322, Georgia, United States.
  • Zhao Y; Department of Surgery and Winship Cancer Institute, Emory University School of Medicine, Atlanta 30322, Georgia, United States.
  • Liu T; Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China.
  • Chen M; Department of Surgery and Winship Cancer Institute, Emory University School of Medicine, Atlanta 30322, Georgia, United States.
  • Qian WP; Department of Surgery and Winship Cancer Institute, Emory University School of Medicine, Atlanta 30322, Georgia, United States.
  • Jiang B; Department of Nuclear Medicine, China-Japan Union Hospital, Jilin University, Changchun 130033, China.
  • Barwick BG; Department of Surgery and Winship Cancer Institute, Emory University School of Medicine, Atlanta 30322, Georgia, United States.
  • Zhang L; Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia 19107, Pennsylvania, United States.
  • Styblo TM; Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta 30322, Georgia, United States.
  • Li X; Department of Surgery and Winship Cancer Institute, Emory University School of Medicine, Atlanta 30322, Georgia, United States.
  • Yang L; Department of Nuclear Medicine, China-Japan Union Hospital, Jilin University, Changchun 130033, China.
ACS Nano ; 16(11): 18708-18728, 2022 11 22.
Article en En | MEDLINE | ID: mdl-36256454
Upregulation of NADPH oxidases (NOXs) in cancer cells leads to chronic increase in intracellular reactive oxygen species (ROS) and adaptation to a high ROS level for cell survival and, thereby, low sensitivity to radiotherapy. To overcome resistance to radiotherapy, we have developed a bioactive and CD44 targeted hyaluronic acid nanoparticle encapsulated with an NOX inhibitor, GKT831 (HANP/GKT831). We found that HANP/GKT831 had stronger inhibitory effects on ROS generation and cell proliferation than that of GKT831 alone in cancer cells. Systemic delivery of HANP/GKT831 led to the targeted accumulation in breast cancer patient derived xenograft (PDX) tumors in nude mice. Importantly, the combination of systemic delivery of HANP/GKT831 with a low dose of local radiotherapy significantly enhanced tumor growth inhibition in breast cancer PDX models. Our results showed that HANP/GKT831 primed tumor cells to radiation-induced DNA damage and cell death by downregulation of DNA repair function and oncogenic signal pathways.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tolerancia a Radiación / Neoplasias de la Mama / Nanopartículas / Ácido Hialurónico Límite: Animals / Female / Humans Idioma: En Revista: ACS Nano Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tolerancia a Radiación / Neoplasias de la Mama / Nanopartículas / Ácido Hialurónico Límite: Animals / Female / Humans Idioma: En Revista: ACS Nano Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos