A novel brachytherapy and chemotherapy integrated ureteral stent: In vitro and in vivo study

Ureteral carcinoma remains a major clinical challenge and requires effective localized treatment. Here, we report a novel ¹²⁵I seed brachytherapy (ISB) and doxorubicin (DOX) chemotherapy integrated ureteral stent (IUS), which enables simultaneous urinary drainage and chemoradiotherapy. This study was divided into three parts. First, ISB and DOX significantly reduced T24 cell viability and inhibited migration and invasion in an in vivo study (<i>p</i> < 0.01). Second, a T24 xenograft mouse model demonstrated that the (DOX + ISB) group exhibited greater tumor suppression than the DOX (<i>p</i> = 0.08) and ISB (<i>p</i> = 0.02) groups, with decreased Ki-67 and Bcl-2 expression and increased apoptosis (all <i>p</i> < 0.01) in an in vitro study. Third, the IUS was successfully implanted in normal beagle dogs (<i>n</i> = 30) without surgical complications. The ureteral diameter increased with increasing cumulative brachytherapy and sustained DOX release (<i>p</i> < 0.05). Histological analysis revealed progressive tissue damage and fibrosis, with increased expression of α-SMA, Caspase-3, and Collagen-1 in the 0.8 mCi + 20 mg DOX group (<i>p</i> < 0.05), whereas PCNA expression was highest in the Control group (0 mCi + 0 mg DOX). In conclusion, the newly designed IUS is safe and technically feasible in animals; clinical studies will be required to evaluate its use in humans.