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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.
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1 College of Life Science and Medicine, Zhejiang Sci-Tech University, Hangzhou, People’s Republic of China
2 Department of Otolaryngology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, People’s Republic of China
3 Department of Biomaterials, College of Materials, Xiamen University, Xiamen, People’s Republic of China