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

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.

Hydrogel: a new material for intravesical drug delivery after bladder cancer surgery

“…However, it had limitations in terms of drug-loading capacity and activity. 69,70 Dong Zhang's team also created a magnetic hydrogel system with targeting ability, improving drug residence time and tumor cell killing while exhibiting irregular drug release. 71 Sylvia Shawky's team designed an adhesive hydrogel composed of chitosan, poloxamer, and solid lipid nanoparticles, which showed prolonged quercetin release in the bladder but had stability issues.…”

“…In vivo research conducted by Chang Zhang, Sun Xiaoliang, Dong Zhang, and others demonstrated stronger anti-tumor efficacy compared to traditional bladder perfusion therapy. [68][69][70][71] However, the poor stability of this material remains a challenge. Sylvia Shawky's team achieved some improvements in the stability by adjusting stabilizer proportions, but there was still a slight size increase in embedded nanoparticles after 3 months.…”

Nano theranostics involved in bladder cancer treatment

“…The study demonstrated that successful magnetic guidance, pH-responsive release, and improved cellular uptake of the NPs led to enhanced chemotherapeutic effects on BC cells. Sun et al [56] designed a magnetic thermosensitive hydrogel, which transformed into a gel and adhered to the bladder wall upon perfusion into the bladder. Due to its sustained release and targeting properties, the hydrogel demonstrated better anti-tumor effects in BC.…”