Tat-functionalized Ag-Fe_3O_4 nano-composites as tissue-penetrating vehicles for tumor magnetic targeting and drug delivery

作     者：Ergang Liu Meng Zhang Hui Cui Junbo Gong Yongzhuo Huang Jianxin Wang Yanna Cui Weibing Dong Lu Sun Huining He Victor C.Yang 

作者机构：State Key Laboratory of Chemical Engineering School of Chemical Engineering and Technology Tianjin University Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnosis School of Pharmacy Tianjin Medical University Shanghai Institute of Materia Medica Chinese Academy of Sciences Department of Pharmaceutics School of Pharmacy Fudan University & Key Laboratory of Smart Drug Delivery Ministry of Education Department of Pharmaceutical Sciences College of Pharmacy University of Michigan 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2018年第8卷第6期

页      面：956-968页

核心收录：

学科分类：100702[医学-药剂学] 1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1001[医学-基础医学(可授医学、理学学位)] 100602[医学-中西医结合临床] 10[医学] 

基　　金：financial supports from National Key Research and Development Plan of China (2016YFE0119200) the Young Elite Scientists Sponsorship Program by Tianjin (No. TJSQNTJ-2017-14) National Natural Science Foundation of China (NSFC 81361140344, 21376164, 81402885, and 81373357) 

主　　题：Cell penetrating peptide Tat Silver nanoparticles Magnetic targeting Fe3O4 Hydrazone bond 

摘      要：In this paper, we prepared a dual functional system based on dextrin-coated silver nanoparticles which were further attached with iron oxide nanoparticles and cell penetrating peptide(Tat), producing Tat-modified Ag-Fe_3O_4 nanocomposites(Tat-FeAgNPs). To load drugs, an –SH containing linker, 3-mercaptopropanohydrazide, was designed and synthesized. It enabled the silver carriers to load and release doxorubicin(Dox) in a pH-sensitive pattern. The delivery efficiency of this system was assessed in vitro using MCF-7 cells, and in vivo using null BalB/c mice bearing MCF-7 xenograft tumors. Our results demonstrated that both Tat and externally applied magnetic field could promote cellular uptake and consequently the cytotoxicity of doxorubicin-loaded nanoparticles,with the IC_(50) of Tat-FeAgNP-Dox to be 0.63 mmol/L. The in vivo delivery efficiency of Tat-FeAgNP carrying Cy5 to the mouse tumor was analyzed using the in vivo optical imaging tests, in which TatFeAgNP-Cy5 yielded the most efficient accumulation in the tumor(6.772.4% ID of Tat-FeAgNPs).Anti-tumor assessment also demonstrated that Tat-FeAgNP-Dox displayed the most significant tumor-inhibiting effects and reduced the specific growth rate of tumor by 29.6%(P ? 0.009), which could be attributed to its superior performance in tumor drug delivery in comparison with the control nanovehicles.