| Autor: |
Jing Sun, Yujie Shi, Gao Xiang, Xin Chen, Qiang Zhang, Lin Zhai, Shi-He Cui, Hong-Gang Qian, Yi Yan, Yuanjun Zhu, Yi Sun, Xiao-Yu Liu, Jiancheng Wang, Cheng-Han Wang, Yi-Da Tang |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Journal of Controlled Release. 339:506-520 |
| ISSN: |
0168-3659 |
| DOI: |
10.1016/j.jconrel.2021.10.012 |
| Popis: |
The combination of nitric oxide (NO) and siRNA is highly desirable for cancer therapy. Here, the furoxans-grafted PEI polymer (FDP) with caspase-3 responsive cleavable DEVD linker was synthesized, and used to bind siRNAs via electrostatic interaction and self-assembled into FDP/siRNA nanoplexes by hydrophobic force. After cellular uptake and lysosomal escape, the FDP/siRNA nanoplexes could achieve GSH-triggered NO release, and then increase the activity of caspase-3. The activated caspase-3 could specifically cleave the DEVD peptide sequence and enhance cell apoptosis. With the cleavage of DEVD peptide sequence, the disassembly of FDP/siRNA nanoplexes was further promoted, thereby resulting in increased siRNAs of ~40% were released at 48 h compared with the caspase-3 non-responsive FDnP/siRNA nanoplexes. By this way, cell apoptosis promotion and cell proliferation inhibition was achieved by siRNA-based downregulation of EGFR protein and the upregulated activity of caspase-3, followed by the enhanced cascade release of NO from FDP/siRNA nanoplexes. Furthermore, in vivo results demonstrated the improved anti-cancer efficiency of FDP/siEGFR nanoplexes without any detectable side effects. Therefore, it is believed that the caspase-3 responsive cleavable furoxans-grafted PEI polymers could provide a potential and efficient enhancement for cancer therapeutic efficiency by the co-delivery of nitric oxide and siRNA. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect