Mastocarcinoma therapy synergistically promoted by lysosome dependent apoptosis specifically evoked by 5-Fu@nanogel system with passive targeting and pH activatable dual function
Mastocarcinoma therapy synergistically promoted by lysosome dependent apoptosis specifically evoked by 5-Fu@nanogel system with passive targeting and pH activatable dual function
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具有被动靶向和 pH 可激活双重功能的 5-Fu@nanogel 系统特异性诱发溶酶体依赖性细胞凋亡，协同促进乳腺癌治疗
DOI：
10.1016/j.jconrel.2017.03.038
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Wei Li
中科院分区：
文献类型：
--
作者：
Xi;i Zhu;Yun Sun;Di Chen;Jingfeng Li;Xia Dong;Jie Wang;Huaiwen Chen;Ying Wang;Fulei Zhang;Jianxin Dai;Rogério P. Pirraco;Shangjing Guo;Alex;ra P. Marques;Rui L. Reis;Wei Li
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.
