Improvement of the bladder perfusion curative effect through tight junction protein degradation induced by magnetic temperature-sensitive hydrogels
Postoperative intravesical instillation of chemotherapy is a routine procedure for non-muscular invasive bladder cancer (NMIBC). However, traditional bladder perfusion methods have insufficient exposure time, resulting in unsatisfactory therapeutic effects. In the present study, a chitosan (CS)-base...
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2022.958072/full |
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| author | Xiaoliang Sun Xinhong Song Peng Guo Dong Zhang Shishuai Zuo Kang Leng Yun Liu Haiyang Zhang Haiyang Zhang Haiyang Zhang |
| author_facet | Xiaoliang Sun Xinhong Song Peng Guo Dong Zhang Shishuai Zuo Kang Leng Yun Liu Haiyang Zhang Haiyang Zhang Haiyang Zhang |
| author_sort | Xiaoliang Sun |
| collection | DOAJ |
| description | Postoperative intravesical instillation of chemotherapy is a routine procedure for non-muscular invasive bladder cancer (NMIBC). However, traditional bladder perfusion methods have insufficient exposure time, resulting in unsatisfactory therapeutic effects. In the present study, a chitosan (CS)-based in situ forming depot (ISFD) delivery system, including Fe3O4 magnetic nanoparticles (Fe3O4-MNP), CS, and β-glycerophosphate (GP) as main components, was synthesized. Pirarubicin (THP), as a chemotherapeutic drug, was loaded into the new system. Results showed that our carrier system (Fe3O4-THP-CS/GP) was converted into gel and attached to the bladder wall, possessing loose network structures with magnetic targeting and sustained release properties. Moreover, its retention time in bladder was more than 72 h accompanied by a suitable expansion rate and good degradation characteristics. The antitumor activities of Fe3O4-THP-CS/GP were more effective both in vitro and in vivo than the free THP solution. In the study of its mechanism, results showed that Fe3O4-THP-CS/GP suppressed the expression of occludin (OCLN) and affected tight junctions (TJ) between urothelial cells to promote THP absorption. |
| first_indexed | 2024-12-11T19:16:07Z |
| format | Article |
| id | doaj.art-dacaa15c87ca4177ab471ebaeb43f524 |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-12-11T19:16:07Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-dacaa15c87ca4177ab471ebaeb43f5242022-12-22T00:53:39ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852022-08-011010.3389/fbioe.2022.958072958072Improvement of the bladder perfusion curative effect through tight junction protein degradation induced by magnetic temperature-sensitive hydrogelsXiaoliang Sun0Xinhong Song1Peng Guo2Dong Zhang3Shishuai Zuo4Kang Leng5Yun Liu6Haiyang Zhang7Haiyang Zhang8Haiyang Zhang9Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Logistics Management, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaKnuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, San Francisco, United StatesPostoperative intravesical instillation of chemotherapy is a routine procedure for non-muscular invasive bladder cancer (NMIBC). However, traditional bladder perfusion methods have insufficient exposure time, resulting in unsatisfactory therapeutic effects. In the present study, a chitosan (CS)-based in situ forming depot (ISFD) delivery system, including Fe3O4 magnetic nanoparticles (Fe3O4-MNP), CS, and β-glycerophosphate (GP) as main components, was synthesized. Pirarubicin (THP), as a chemotherapeutic drug, was loaded into the new system. Results showed that our carrier system (Fe3O4-THP-CS/GP) was converted into gel and attached to the bladder wall, possessing loose network structures with magnetic targeting and sustained release properties. Moreover, its retention time in bladder was more than 72 h accompanied by a suitable expansion rate and good degradation characteristics. The antitumor activities of Fe3O4-THP-CS/GP were more effective both in vitro and in vivo than the free THP solution. In the study of its mechanism, results showed that Fe3O4-THP-CS/GP suppressed the expression of occludin (OCLN) and affected tight junctions (TJ) between urothelial cells to promote THP absorption.https://www.frontiersin.org/articles/10.3389/fbioe.2022.958072/fullbladder perfusionpirarubicinchitosansustained releasetight junctionoccludin |
| spellingShingle | Xiaoliang Sun Xinhong Song Peng Guo Dong Zhang Shishuai Zuo Kang Leng Yun Liu Haiyang Zhang Haiyang Zhang Haiyang Zhang Improvement of the bladder perfusion curative effect through tight junction protein degradation induced by magnetic temperature-sensitive hydrogels Frontiers in Bioengineering and Biotechnology bladder perfusion pirarubicin chitosan sustained release tight junction occludin |
| title | Improvement of the bladder perfusion curative effect through tight junction protein degradation induced by magnetic temperature-sensitive hydrogels |
| title_full | Improvement of the bladder perfusion curative effect through tight junction protein degradation induced by magnetic temperature-sensitive hydrogels |
| title_fullStr | Improvement of the bladder perfusion curative effect through tight junction protein degradation induced by magnetic temperature-sensitive hydrogels |
| title_full_unstemmed | Improvement of the bladder perfusion curative effect through tight junction protein degradation induced by magnetic temperature-sensitive hydrogels |
| title_short | Improvement of the bladder perfusion curative effect through tight junction protein degradation induced by magnetic temperature-sensitive hydrogels |
| title_sort | improvement of the bladder perfusion curative effect through tight junction protein degradation induced by magnetic temperature sensitive hydrogels |
| topic | bladder perfusion pirarubicin chitosan sustained release tight junction occludin |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2022.958072/full |
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