A high affinity kidney targeting by chitobionic acid-conjugated polysorbitol gene transporter alleviates unilateral ureteral obstruction in rats

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• 作者：Mohammad Ariful Islam^a ; ^b ; ¹ ; Sanghwa Kim^c ; ^g ; ¹ ; Jannatul Firdous^a ; ^b ; Ah-Young Lee^c ; Seong-Ho Hong^c ; Min Kyeong Seo^c ; Tae-Eun Park^b ; ^d ; Cheol-Heui Yun^b ; Yun-Jaie Choi^b ; Chanhee Chae^e ; Chong-Su Cho^b ; ^{chocs@snu.ac.kr" class="auth_mail" title="E-mail the corresponding author} ; Myung-Haing Cho^c ; ^f ; ^g ; ^h ; ⁱ ; ^{mchotox@snu.ac.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Chitobionic acid ; Polysorbitol gene transporter ; HGF ; Kidney targeting ; UUO
• 刊名：Biomaterials
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：102
• 期：Complete
• 页码：43-57
• 全文大小：4235 K

文摘

Aside from kidney transplantation – a procedure which is exceedingly dependent on donor-match and availability leading to excessive costs – there are currently no permanent treatments available which reverse kidney injury and failure. However, kidney-specific targeted gene therapy has outstanding potential to treat kidney-related dysfunction. Herein we report a novel kidney-specific targeted gene delivery system developed through the conjugation of chitobionic acid (CBA) to a polysorbitol gene transporter (PSGT) synthesized from sorbitol diacrylate and low molecular weight polyethylenimine (PEI) carrying hepatocyte growth factor (HGF) gene to alleviate unilateral ureteral obstruction (UUO) in rats. CBA-PSGT performed exceptionally well for targeted delivery of HGF to kidney tissues compared to its non-targeted counterparts (P < 0.001) after systemic tail-vein injection and significantly reduced the UUO symptoms, returning the UUO rats to a normal health status. The kidney-targeted CBA-PSGT-delivered HGF also strikingly reduced various pathologic and molecular markers in vivo such as the level of collagens (type I and II), blood urea nitrogen (BUN), creatinine, and the expressions of ICAM-1, TIMP-1 and α-SMA which play a critical role in obstructive kidney functions. Therefore, CBA-PSGT should be further investigated because of its potential to alleviate UUO and kidney-related diseases using high affinity kidney targeting.