A high affinity kidney targeting by chitobionic acid-conjugated polysorbitol gene transporter alleviates unilateral ureteral obstruction in rats
| Autor: | Chong-Su Cho, Sang Wha Kim, Ah-Young Lee, Yun-Jaie Choi, Tae-Eun Park, Seong-Ho Hong, Mohammad Ariful Islam, Cheol-Heui Yun, Min Kyeong Seo, Myung-Haing Cho, Chanhee Chae, Jannatul Firdous |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Genetic enhancement Biophysics Bioengineering Gene delivery Pharmacology Biology Disaccharides Kidney Cell Line Rats Sprague-Dawley Biomaterials 03 medical and health sciences chemistry.chemical_compound Internal medicine medicine Animals Humans Polyethyleneimine Sorbitol Blood urea nitrogen Kidney transplantation Mice Inbred BALB C Creatinine Hepatocyte Growth Factor urogenital system Gene Transfer Techniques Sugar Acids Transporter DNA medicine.disease Rats 030104 developmental biology Endocrinology medicine.anatomical_structure chemistry Mechanics of Materials Ceramics and Composites Hepatocyte growth factor Ureteral Obstruction medicine.drug |
| Zdroj: | Biomaterials. 102:43-57 |
| ISSN: | 0142-9612 |
| DOI: | 10.1016/j.biomaterials.2016.06.013 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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