https://scholars.lib.ntu.edu.tw/handle/123456789/629767
標題: | Supramolecular hydrogel for programmable delivery of therapeutics to cancer multidrug resistance | 作者: | Chen, Liang-Hsin Liang, Nai-Wen Huang, Wei-Yuan Liu, Yu-Chung Ho, Chia-Yu CHEN-HSIANG KUAN Huang, Yu-Fen Wang, Tzu-Wei |
關鍵字: | Cancer therapy; DNA complementary; Multidrug resistance; RNA interference; Self-assembly | 公開日期: | 三月-2023 | 卷: | 146 | 來源出版物: | Biomaterials advances | 摘要: | Multidrug resistance (MDR) has been considered as a major adversary in oncologic chemotherapy. To simultaneously overcome drug resistance and inhibit tumor growth, it is essential to develop a drug delivery system that can carry and release multiple therapeutic agents with spatiotemporal control. In this study, we developed a hydrogel containing an enzyme-cleavable peptide motif, with a network structure formed by 4-armed polyethylene glycol (PEG) crosslinked by complementary nucleic acid sequences. Hydrogen bond formation between nucleobase pairing allows the hydrogel to be injectable, and the peptide motif grants deliberate control over hydrogel degradation and the responsive drug release. Moreover, MDR-targeted siRNAs are complexed with stearyl-octaarginine (STR-R8), while doxorubicin (Dox) is intercalated with DNA and nanoclay structures in this hydrogel to enhance therapeutic efficacy and overcome MDR. The results show a successful configuration of a hydrogel network with in situ gelation property, injectability, and degradability in the presence of tumor-associated enzyme, MMP-2. The synergistic effect by combining MDR-targeted siRNAs and Dox manifests with the enhanced anti-cancer effect on drug resistant breast cancer cells in both in vitro and in vivo tumor models. We suggest that with the tailor-designed hydrogel system, multidrug resistance in tumor cells can be significantly inhibited by the co-delivery of multiple therapeutics with spatial-temporal control release. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/629767 | ISSN: | 27729508 | DOI: | 10.1016/j.bioadv.2023.213282 |
顯示於: | 醫學系 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。