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Detachable MOF-Based Core/Shell Nanoreactor for Cancer Dual-Starvation Therapy With Reversing Glucose and Glutamine Metabolisms.
Du, Huiping; Meng, Siyu; Geng, Meijuan; Zhao, Pan; Gong, Liyang; Zheng, Xinmin; Li, Xiang; Yuan, Zhang; Yang, Hui; Zhao, Yanli; Dai, Liangliang.
Afiliación
  • Du H; Xi'an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University, Xi'an, 710072, P. R. China.
  • Meng S; Xi'an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University, Xi'an, 710072, P. R. China.
  • Geng M; Xi'an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University, Xi'an, 710072, P. R. China.
  • Zhao P; Xi'an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University, Xi'an, 710072, P. R. China.
  • Gong L; Xi'an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University, Xi'an, 710072, P. R. China.
  • Zheng X; School of Life Science, Northwestern Polytechnical University, Xian, 710072, China.
  • Li X; School of Life Science, Northwestern Polytechnical University, Xian, 710072, China.
  • Yuan Z; Xi'an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University, Xi'an, 710072, P. R. China.
  • Yang H; School of Life Science, Northwestern Polytechnical University, Xian, 710072, China.
  • Zhao Y; School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 21 Nanyang Link, Singapore, 637371, Singapore.
  • Dai L; Xi'an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University, Xi'an, 710072, P. R. China.
Small ; 19(42): e2303253, 2023 10.
Article en En | MEDLINE | ID: mdl-37330663
Tumor-dependent glucose and glutamine metabolisms are essential for maintaining survival, while the accordingly metabolic suppressive therapy is limited by the compensatory metabolism and inefficient delivery efficiency. Herein, a functional metal-organic framework (MOF)-based nanosystem composed of the weakly acidic tumor microenvironment-activated detachable shell and reactive oxygen species (ROS)-responsive disassembled MOF nanoreactor core is designed to co-load glycolysis and glutamine metabolism inhibitors glucose oxidase (GOD) and bis-2-(5-phenylacetmido-1,2,4-thiadiazol-2-yl) ethyl sulfide (BPTES) for tumor dual-starvation therapy. The nanosystem excitingly improves tumor penetration and cellular uptake efficiency via integrating the pH-responsive size reduction and charge reversal and ROS-sensitive MOF disintegration and drug release strategy. Furthermore, the degradation of MOF and cargoes release can be self-amplified via additional self-generation H2 O2 mediated by GOD. Last, the released GOD and BPTES collaboratively cut off the energy supply of tumors and induce significant mitochondrial damage and cell cycle arrest via simultaneous restriction of glycolysis and compensatory glutamine metabolism pathways, consequently realizing the remarkable triple negative breast cancer killing effect in vivo with good biosafety via the dual starvation therapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Estructuras Metalorgánicas / Neoplasias Límite: Humans Idioma: En Revista: Small Asunto de la revista: ENGENHARIA BIOMEDICA Año: 2023 Tipo del documento: Article Pais de publicación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Estructuras Metalorgánicas / Neoplasias Límite: Humans Idioma: En Revista: Small Asunto de la revista: ENGENHARIA BIOMEDICA Año: 2023 Tipo del documento: Article Pais de publicación: Alemania