Bioreducible Zinc(II)-Dipicolylamine Functionalized Hyaluronic Acid Mediates Safe siRNA Delivery and Effective Glioblastoma RNAi Therapy
| Autor: | Zhipeng Yang, Haigang Wu, Jeng-Wei Lu, Xing-Jie Liang, Amanda L. Wright, Albert Lee, Xue Xia, Meng Zheng, Yingze Wang, Shizhu Chen, Yang Liu, Jinchao Zhang, Huijun Yin, Weimin Ruan |
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| Rok vydání: | 2022 |
| Předmět: |
Small interfering RNA
010405 organic chemistry Chemistry Genetic enhancement Biochemistry (medical) Biomedical Engineering chemistry.chemical_element 02 engineering and technology General Chemistry Zinc 021001 nanoscience & nanotechnology medicine.disease 01 natural sciences 0104 chemical sciences Biomaterials chemistry.chemical_compound Dipicolylamine RNA interference Hyaluronic acid medicine Cancer research Delivery system 0210 nano-technology Glioblastoma |
| Zdroj: | ACS applied bio materials. 2(1) |
| ISSN: | 2576-6422 |
| Popis: | RNA interference (RNAi) is an emerging therapeutic modality for tumors. However, lack of a safe and efficient small interfering RNA (siRNA) delivery system limits its clinical application. Here, we report a bioreducible and less-cationic siRNA delivery carrier by conjugating Zn(II)-dipicolylamine complexes (Zn-DPA) onto hyaluronic acid (HA) via a redox-sensitive disulfide (-SS-) linker. Such polymer conjugates can formulate stable siRNA nanomedicines via coordination between zinc ions of DPA and the anionic phosphate of siRNA. After the conjugates are taken up by cells, intracellular reduction stimulus subsequently triggers the release of siRNAs and elucidates the desired RNAi effect. Our studies showed the formulated siRNA nanomedicines can be efficiently delivered into tumor cells/tissues and mediates less cytotoxicities both in vitro and in vivo. More importantly, when applied in a xenograft glioblastoma tumor model, this siRNA nanomedicine demonstrated significantly enhanced antitumor ability comparing to naked siRNA. This work demonstrates that such bioreducible Zn-DPA-functionalized HA conjugates without using cationic material as a siRNA carrier represents a promising direction for RNAi-based cancer therapy. |
| Databáze: | OpenAIRE |
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