ArticleInternational journal of nanomedicine2026
Targeted Nanoparticles for PROTAC-Mediated JAK1/JAK2 Degradation for Bladder Cancer Treatment.
Article in International journal of nanomedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Purpose: Although inhibition of the JAK-STAT signaling pathway has shown promise in cancer therapy, the therapeutic potential of PROTAC-mediated JAK1/JAK2 degradation in bladder cancer remains to be fully explored. To improve the delivery and therapeutic efficacy of PROTAC-mediated JAK1/JAK2 degradation in bladder cancer, this study developed PPcJ, a cRGD-functionalized PLGA-PEG nanoparticle encapsulating the PROTAC-based JAK1/JAK2 degrader JAPT8. Methods: PPcJ nanoparticles were characterized using transmission electron microscopy, dynamic light scattering, and high-performance liquid chromatography. Flow cytometry and confocal microscopy were used to evaluate cytotoxicity, anti-tumor effect, and intracellular localization, while Western blotting assessed the expression of JAK/STAT pathway and apoptosis-related proteins. In vivo tumor-associated fluorescence, antitumor efficacy, survival, histopathology, and serum biochemical parameters were assessed in tumor-bearing mice. Results: PPcJ exhibited a spherical nanoscale morphology. PPcJ achieved near-plateau cellular uptake at low concentrations and partially evaded lysosomal degradation, which significantly induced apoptosis in bladder cancer cells and suppressed key components of the JAK/STAT signaling pathway. In vivo, cRGD modification enabled higher tumor-specific accumulation and prolonged retention. PPcJ inhibited tumor growth by 86.2% and prolonged mean survival from 22.4 ± 4.2 to 41.0 ± 2.2 days, without significant changes in body weight, major-organ histology, or serum AST, ALT, urea, and creatinine levels under the tested conditions. Conclusion: These findings provide a preclinical proof-of-concept that the PPcJ nano-delivery system improves the delivery and antitumor performance of JAPT8. This strategy warrants further evaluation in systemic therapeutic approaches for bladder cancer.
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