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Intracellular Restructured Reduced Glutathione-Responsive Peptide Nanofibers for Synergetic Tumor Chemotherapy.
Biomacromolecules ( IF 6.2 ) Pub Date : 2020-01-08 , DOI: 10.1021/acs.biomac.9b01202
Wang-Wei Guo , Zhen-Tao Zhang , QiChun Wei , Yi Zhou , Meng-Ting Lin , Jie-Jian Chen , Tian-Tian Wang , Ning-Ning Guo , Xin-Cheng Zhong , Yi-Ying Lu , Qi-Yao Yang , Min Han , JianQing Gao

Self-assembled peptide nanofibers have been widely studied in cancer nanotherapeutics with their excellent biocompatibility and low toxicity of degradation products, showing the significant potential in inhibiting tumor progression. However, poor solubility prevents direct intravenous administration of nanofibers. Although water-soluble peptide precursors have been formed via the method of phosphorylation for intravenous administration, their opportunities for broad in vivo application are limited by the weak capacity of encapsulating drugs. Herein, we designed a novel restructured reduced glutathione (GSH)-responsive drug delivery system encapsulating doxorubicin for systemic administration, which achieved the intracellular restructuration from three-dimensional micelles into one-dimensional nanofibers. After a long blood circulation, micelles endocytosed by tumor cells could degrade in response to high GSH levels, achieving more release and accumulation of doxorubicin at desired sites. Further, the synergistic chemotherapy effects of self-assembled nanofibers were confirmed in both in vitro and in vivo experiments.

中文翻译:

细胞内重组减少的谷胱甘肽反应性肽纳米纤维的协同肿瘤化学疗法。

自组装肽纳米纤维以其优异的生物相容性和降解产物的低毒性在癌症纳米治疗中得到了广泛的研究,显示出抑制肿瘤进展的巨大潜力。但是,不良的溶解性阻止了纳米纤维的直接静脉内给药。尽管已经通过用于静脉内施用的磷酸化方法形成了水溶性肽前体,但是其包囊药物的弱能力限制了它​​们在体内广泛应用的机会。在这里,我们设计了一种新型的重组还原型谷胱甘肽(GSH)响应型药物递送系统,该系统封装了阿霉素用于全身给药,从而实现了从三维胶束到一维纳米纤维的细胞内重构。经过长时间的血液循环,肿瘤细胞内吞的胶束可响应高GSH水平而降解,从而在所需部位实现更多的阿霉素释放和积累。此外,在体外和体内实验中均证实了自组装纳米纤维的协同化疗作用。
更新日期:2020-01-09
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