Jinxia Zhang, 1, 2, Xinxin Xie, 2, Yuanjing Li, 1, Haonan Wang, 2 Lijuan Zhang, 1 Peiqi Shi, 1 Jing Wei, 1 Ling Zhang, 1 Yingdong Lu, 1 Ligang Cui, 2 Xiaoning Liu, 1 Xiaolong Liang2 1Department of Ultrasound, Guangâanmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, Peopleâs Republic of China; 2Department of Ultrasound, Peking University Third Hospital, Beijing, 100191, Peopleâs Republic of ChinaThese authors contributed equally to this workCorrespondence: Xiaoning Liu, Email liuxnₐngel2023@163. com Xiaolong Liang, Email xiaolongₗiang@bjmu. edu. cnIntroduction: Emodin alleviates renal interstitial fibrosis (RIF) and reduces inflammation by inhibiting the TGF-β 1/Smad pathway, thus improving CKD outcomes. However, its clinical use is limited due to poor solubility and side effects. This study developed a targeted drug delivery system using αKIM-1 modified microbubbles carrying Emodin to enhance accumulation in renal tissues with high KIM-1 expression. Methods: Emo@KP MBs were characterized by TEM and DLS, and their drug loading and encapsulation rates were measured by UV-VIS-NIR spectroscopy. Biocompatibility was assessed in vitro with HK-2 cells and in vivo via hematological and pathological markers. Contrast-enhanced ultrasound (CEUS) and fluorescence imaging were used for real-time visualization of treatment. Therapeutic experiments were performed on a unilateral ureteral obstruction (UUO) mouse model treated with Emo@KP MBs + US on days 1 and 3 post-surgery. Renal function, cytokine levels, and histological analysis were detected to evaluate therapeutic effects. Results: Emo@KP MBs exhibited spherical structures (2 ~ 4 μm) with good stability. Ultrasound targeted microbubble destruction (UTMD) enabled controlled release of Emodin. CEUS and fluorescence imaging showed enhanced drug accumulation in diseased kidneys. In the UUO + Emo@KP MBs/US group, renal function was improved, inflammatory cytokines (IL-1β, TNF-α) were decreased, and renal lesions and collagen deposition were reduced. Immunohistochemistry revealed the downregulation of TGF-β, Smad2/3, and α-SMA, and upregulation of E-cadherin. Conclusion: Emo@KP MBs enhanced drug delivery efficiency and therapeutic efficacy through αKIM-1 targeting and UTMD, while providing real-time imaging capabilities, suggesting good potential as a therapeutic approach to reduce renal inflammation and fibrosis in UUO. Keywords: unilateral ureteral obstruction, renal interstitial fibrosis, microbubbles, UTMD, Emodin, αKIM-1
Zhang et al. (Mon,) studied this question.