Nanoparticle-mediated intravesical delivery of conditioned medium derived from mesenchymal stem cells for interstitial cystitis/bladder pain syndrome treatment

• PLGA-TMC NPs-assisted intravesical delivery of CM improves the therapeutic effect for IC/BPS. • The TMC coating enhances the accumulation of CM-loaded nanoparticles in the urothelium and subsequently improves the therapeutic efficacy. • The therapeutic efficacy of CM exerts on the mechanical threshold and micturition function through facilitating the effect of anti-inflammation and BDNF/TrkB signaling. Interstitial cystitis/bladder pain syndrome (IC/BPS) is a critical disease characterized by debilitating pelvic pain associated with lower urinary tract symptoms. Effective therapeutic strategies remain challenging due to their elusive pathogenesis. Mesenchymal stem cell (MSC) therapy offers a promising therapeutic approach for IC/BPS treatment. Yet, the ethical arguments and tumorigenic risks from cell therapy by stem cells restrict the clinical application. Herein, we developed a nanoparticle that encapsulates the conditioned medium (CM) from stem cells and coated with cationic N-trimethyl chitosan chloride (TMC) on the surface to improve the penetration of epithelial barrier in intravesical therapy for IC/BPS. The TMC coating enhanced the accumulation of CM-loaded nanoparticles in the urothelium and subsequently improved the therapeutic efficacy on the mechanical threshold and micturition function through facilitating the effect of anti-inflammation and BDNF/TrkB signaling, which provides a great potential application on the transmucosal delivery platform for intravesical therapy of IC/BPS.