Improvement of the bladder perfusion curative effect through tight junction protein degradation induced by magnetic temperature-sensitive hydrogels

Xiaoliang Sun; Xinhong Song; Peng Guo; Dong Zhang; Shishuai Zuo; Kang Leng; Yun Liu; Haiyang Zhang

doi:10.3389/fbioe.2022.958072

Improvement of the bladder perfusion curative effect through tight junction protein degradation induced by magnetic temperature-sensitive hydrogels

Front Bioeng Biotechnol. 2022 Aug 4:10:958072. doi: 10.3389/fbioe.2022.958072. eCollection 2022.

Authors

Xiaoliang Sun¹, Xinhong Song², Peng Guo¹, Dong Zhang¹, Shishuai Zuo¹, Kang Leng¹, Yun Liu¹, Haiyang Zhang^{1

3

4}

Affiliations

¹ Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
² Department of Logistics Management, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
³ Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
⁴ Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, San Francisco, United States.

Abstract

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.

Keywords: bladder perfusion; chitosan; occludin; pirarubicin; sustained release; tight junction.