Tat-functionalized Ag-FeO nano-composites as tissue-penetrating vehicles for tumor magnetic targeting and drug delivery.
10.1016/j.apsb.2018.07.012
- Author:
Ergang LIU
1
;
Meng ZHANG
2
;
Hui CUI
3
;
Junbo GONG
1
;
Yongzhuo HUANG
2
;
Jianxin WANG
4
;
Yanna CUI
2
;
Weibing DONG
1
;
Lu SUN
3
;
Huining HE
3
;
Victor C YANG
1
Author Information
1. State Key Laboratory of Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.
2. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
3. Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnosis, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
4. Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai 201203, China.
- Publication Type:Journal Article
- Keywords:
Cell penetrating peptide;
Fe3O4;
Hydrazone bond;
Magnetic targeting;
Silver nanoparticles;
Tat
- From:
Acta Pharmaceutica Sinica B
2018;8(6):956-968
- CountryChina
- Language:English
-
Abstract:
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-FeO 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 using MCF-7 cells, and 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 of Tat-FeAgNP-Dox to be 0.63 µmol/L. The delivery efficiency of Tat-FeAgNP carrying Cy5 to the mouse tumor was analyzed using the optical imaging tests, in which Tat-FeAgNP-Cy5 yielded the most efficient accumulation in the tumor (6.7±2.4% 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% ( = 0.009), which could be attributed to its superior performance in tumor drug delivery in comparison with the control nanovehicles.
