Abstract

RNA interference (RNAi) has potential advantages over other gene therapy approaches due to its high specificity and the ability to inhibit target gene expression. However, the stability and tissue-specific delivery of siRNA remain as the biggest obstacles for RNAi therapeutics. Here, we developed such a system by conjugating gelatin-based nanogels with the nucleolin-targeted AS1411 aptamer and deoxynucleotide-substituted siRNA together (Apt-GS/siRNA) via a disulfide linker to achieve transient docking of siRNA. These Apt-GS/siRNA nanogels demonstrated favorable release of siRNA under reducing conditions owing to disulfide cleavage. Furthermore, this smart system could electively release siRNA into the cytosol in nucleolin-positive cells (A549) by a glutathione-triggered disassembly and subsequently efficient RNAi for luciferase. Besides, disulfide-equipped Apt-GS nanogels showed good biocompatibility in vitro. Taken together, this redox-responsive, tumor-targeting smart nanogels display great potential in exploiting functionalized siRNA delivery and tumor therapy.

Details

Title
Redox-Sensitive Gelatin/Silica-Aptamer Nanogels for Targeted siRNA Delivery
Author
Zhao, Xueqin 1   VIAFID ORCID Logo  ; Xi, Yinyin 1 ; Zhang, Yongming 1 ; Wu, Qiuyan 1 ; Meng, Ruiyuan 1 ; Zheng, Bin 2 ; Lei Rei 3 

 College of Life Science and Medicine, Zhejiang Sci-Tech University, Hangzhou, People’s Republic of China 
 Department of Otolaryngology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, People’s Republic of China 
 Department of Biomaterials, College of Materials, Xiamen University, Xiamen, People’s Republic of China 
Pages
1-9
Publication year
2019
Publication date
Aug 2019
Publisher
Springer Nature B.V.
ISSN
19317573
e-ISSN
1556276X
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2273097446
Copyright
Nanoscale Research Letters is a copyright of Springer, (2019). All Rights Reserved., © 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.