Interstitial cystitis (IC), as a representative bladder pain syndrome (BPS), is a complex chronic disorder characterized by debilitating pain in the lower abdomen, lower urinary tract, and pelvic area. Unfortunately, there is no cure by far for IC, with a scarcity of effective diagnostic and therapeutic regimens due to the unelucidated pathogenesis. Herein, we propose a versatile theranostic NADC that comprises covalently-coupled monoclonal antibodies (Tanezumab, Tan) targeting the never grow factor (NGF), near-infrared (NIR) fluorescent gold quantum clusters (AuQCs), and the potent dihydroorotate dehydrogenase (DHODH) inhibitor Vidofludimus (Vido). We systemically characterized the derived NADC. The Tan-AuQCs-Vido NADC coordinately regulated pro- and anti-inflammatory cytokines in the human urothelium cell (SV-HUC-1) model of IC. Furthermore, time-course in vivo fluorescence imaging disclosed prolonged bladder retention of NADC in an IC rat model compared to AuQCs. This study presented a state-of-art NADC framework for diagnosing and treating IC patients with high NGF expressions in bladder mucosae. Moreover, intravesical instillation improved the therapeutic efficacy on the mechanical threshold and micturition function, serving as a precision theranostic agent with translational potentials.

Intravesical delivery of nanocluster-antibody-drug-conjugates (NADC) for precision theranostics of interstitial cystitis

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ACS Fall 2022

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