ROS-responsive nano-drug delivery system combining mitochondria-targeting ceria nanoparticles with atorvastatin for acute kidney injury
| Autor: | Jing Qi, Saiping Jiang, Mingchen Sun, Ping Yang, Xiao-Juan Wang, Yong-Zhong Du, Feiyang Jin, Di Liu, Hui Yu, Gaofeng Shu, Xiao-Ying Ying |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Antioxidant
Polyesters medicine.medical_treatment Atorvastatin Medicine (miscellaneous) Apoptosis 02 engineering and technology Pharmacology Mitochondrion 010402 general chemistry medicine.disease_cause 01 natural sciences Antioxidants Polyethylene Glycols Mice Drug Delivery Systems Organophosphorus Compounds Polylactic Acid-Polyglycolic Acid Copolymer In vivo Human Umbilical Vein Endothelial Cells medicine Animals Humans mitochondria-targeting Pharmacology Toxicology and Pharmaceutics (miscellaneous) chemistry.chemical_classification Reactive oxygen species technology industry and agriculture Acute kidney injury Cerium Acute Kidney Injury 021001 nanoscience & nanotechnology medicine.disease ROS-responsive Mitochondria ceria 0104 chemical sciences Drug Liberation Oxidative Stress chemistry Nanoparticles Reactive Oxygen Species 0210 nano-technology Oxidative stress Research Paper medicine.drug |
| Zdroj: | Theranostics |
| ISSN: | 1838-7640 |
| Popis: | Acute kidney injury (AKI) caused by sepsis is a serious disease which mitochondrial oxidative stress and inflammatory play a key role in its pathophysiology. Ceria nanoparticles hold strong and recyclable reactive oxygen species (ROS)-scavenging activity, have been applied to treat ROS-related diseases. However, ceria nanoparticles can't selectively target mitochondria and the ultra-small ceria nanoparticles are easily agglomerated. To overcome these shortcomings and improve therapeutic efficiency, we designed an ROS-responsive nano-drug delivery system combining mitochondria-targeting ceria nanoparticles with atorvastatin for acute kidney injury. Methods: Ceria nanoparticles were modified with triphenylphosphine (TCeria NPs), followed by coating with ROS-responsive organic polymer (mPEG-TK-PLGA) and loaded atorvastatin (Atv/PTP-TCeria NPs). The physicochemical properties, in vitro drug release profiles, mitochondria-targeting ability, in vitro antioxidant, anti-apoptotic activity and in vivo treatment efficacy of Atv/PTP-TCeria NPs were examined. Results: Atv/PTP-TCeria NPs could accumulate in kidneys and hold a great ability to ROS-responsively release drug and TCeria NPs could target mitochondria to eliminate excessive ROS. In vitro study suggested Atv/PTP-TCeria NPs exhibited superior antioxidant and anti-apoptotic activity. In vivo study showed that Atv/PTP-TCeria NPs effectively decreased oxidative stress and inflammatory, could protect the mitochondrial structure, reduced apoptosis of tubular cell and tubular necrosis in the sepsis-induced AKI mice model. Conclusions: This ROS-responsive nano-drug delivery system combining mitochondria-targeting ceria nanoparticles with atorvastatin has favorable potentials in the sepsis-induced AKI therapy. |
| Databáze: | OpenAIRE |
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