| Autor: |
Suchen Bian, Haijiang Dong, Long Zhao, Zequn Li, Jian Chen, Xingxin Zhu, Nasha Qiu, Xing Jia, Wenfeng Song, Zekuan Li, Shusen Zheng, Hangxiang Wang, Penghong Song |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Advanced Science, Vol 9, Iss 29, Pp n/a-n/a (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2198-3844 |
| DOI: |
10.1002/advs.202201931 |
| Popis: |
Abstract Pancreatic ductal adenocarcinoma (PDAC), one of the worst prognosis types of tumors, is characterized by dense extracellular matrix, which compresses tumor vessels and forms a physical barrier to inhibit therapeutic drug penetration and efficacy. Herein, losartan, an antihypertension agent, is applied as a tumor stroma modulator and developed into a nanosystem. A series of lipophilic losartan prodrugs are constructed by esterification of the hydroxyl group on losartan to fatty acids. Based on the self‐assembly ability and hydrodynamic diameter, the losartan‐linoleic acid conjugate is selected for further investigation. To improve the stability in vivo, nanoassemblies are refined with PEGylation to form losartan nanoblocker (Los NB), and administered via intravenous injection for experiments. On murine models of pancreatic cancer, Los NB shows a greater ability to remodel the tumor microenvironment than free losartan, including stromal depletion, vessel perfusion increase, and hypoxia relief. Furthermore, Los NB pretreatment remarkably enhances the accumulation and penetration of 7‐ethyl‐10‐hydroxycamptothecin (SN38)‐loaded nanodrugs (SN38 NPs) in tumor tissues. Expectedly, overall therapeutic efficacy of SN38 NPs is significantly enhanced after Los NB pretreatment. Since losartan is one of the most commonly used antihypertension agents, this study may provide a potential for clinical transformation in stroma‐rich PDAC treatment. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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