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Mastocarcinoma therapy synergistically promoted by lysosome dependent apoptosis specifically evoked by 5-Fu@nanogel system with passive targeting and pH activatable dual function.
Zhu, Xiandi; Sun, Yn; Chen, Di; Li, Jingfeng; Dong, Xia; Wang, Jie; Chen, Huaiwen; Wang, Ying; Zhang, Fulei; Dai, Jinaxin; Pirraco, Rogério P; Guo, Shangjing; Marques, Alexandra P; Reis, Rui L; Li, Wei.
Afiliación
  • Zhu X; International Joint Cancer Institute, The Second Military Medical University, Shanghai 200433, China.
  • Sun Y; International Joint Cancer Institute, The Second Military Medical University, Shanghai 200433, China.
  • Chen D; International Joint Cancer Institute, The Second Military Medical University, Shanghai 200433, China.
  • Li J; International Joint Cancer Institute, The Second Military Medical University, Shanghai 200433, China.
  • Dong X; International Joint Cancer Institute, The Second Military Medical University, Shanghai 200433, China.
  • Wang J; International Joint Cancer Institute, The Second Military Medical University, Shanghai 200433, China; College of Pharmacy, Liaocheng University, 1Hunan Road, Liaocheng, Shandong 25000, China.
  • Chen H; International Joint Cancer Institute, The Second Military Medical University, Shanghai 200433, China.
  • Wang Y; International Joint Cancer Institute, The Second Military Medical University, Shanghai 200433, China.
  • Zhang F; International Joint Cancer Institute, The Second Military Medical University, Shanghai 200433, China.
  • Dai J; International Joint Cancer Institute, The Second Military Medical University, Shanghai 200433, China.
  • Pirraco RP; 3B's Research Group-Biomaterials, Biodegradables, and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal; ICVS-3B's-PT Government Associate Laboratory, Braga, Guimarães, Portugal.
  • Guo S; College of Pharmacy, Liaocheng University, 1Hunan Road, Liaocheng, Shandong 25000, China.
  • Marques AP; 3B's Research Group-Biomaterials, Biodegradables, and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal; ICVS-3B's-PT Government Associate Laboratory, Braga, Guimarães, Portugal.
  • Reis RL; 3B's Research Group-Biomaterials, Biodegradables, and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal; ICVS-3B's-PT Government Associate Laboratory, Braga, Guimarães, Portugal.
  • Li W; International Joint Cancer Institute, The Second Military Medical University, Shanghai 200433, China; College of Pharmacy, Liaocheng University, 1Hunan Road, Liaocheng, Shandong 25000, China. Electronic address: liwei@smmu.edu.cn.
J Control Release ; 254: 107-118, 2017 05 28.
Article en En | MEDLINE | ID: mdl-28342982
This manuscript describes a synergistic therapy for mastocarcinoma by pH and temperature dual-sensitive nanogel, and effects of microstructure, composition and properties of nanogel on the cellular response mechanism. The extracellular internalization of nanogels was obviously enhanced, due to the passive targeting function at T>VPTT. Interestingly, the increased cytotoxicity was further synergistically enhanced by an unexpected apoptosis as evoked by the 5-fluorouracil loaded nanogel (FLNG). The systemically evaluation of the effectors generated from different sub-cellular organelles including endosome, lysosome, autophagosome confirmed that it was a lysomal dependent apoptosis. Such specific apoptosis was mainly attributed to its activatable protonated PEI at low pH, which caused lysosomal membrane destruction and lysosomal enzyme cathepsin B (Cat B) leakage. This Cat B was then translocated to the mitochondria resulting in mitochondrial membrane permeability increase and mitochondrial membrane potential (MMP) decrease, followed by cytochrome c (Cyt C) release. Cyt C was the main molecule that evoked apoptosis as reflected by overexpression of caspase 9. Additionally, such lysosome dependent, apoptosis was further enhanced by the passive cellular targeting at T>VPTT. Thus, the tumor growth inhibition was synergistically enhanced by the extracellular temperature dependent passive targeting and intracellular pH activatable lysosomal dependent apoptosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Apoptosis / Nanoestructuras / Fluorouracilo / Lisosomas / Antineoplásicos Límite: Animals / Female / Humans Idioma: En Revista: J Control Release Asunto de la revista: FARMACOLOGIA Año: 2017 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Apoptosis / Nanoestructuras / Fluorouracilo / Lisosomas / Antineoplásicos Límite: Animals / Female / Humans Idioma: En Revista: J Control Release Asunto de la revista: FARMACOLOGIA Año: 2017 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos