AuCePt porous hollow cascade nanozymes targeted delivery of disulfiram for alleviating hepatic insulin resistance
Abstract As the pathophysiological basis of type 2 diabetes mellitus (T2DM), insulin resistance (IR) is closely related to oxidative stress (OS) and inflammation, while nanozymes have a good therapeutic effect on inflammation and OS by scavenging reactive oxygen species (ROS). Hence, AuCePt porous h...
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2024-10-01
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| Online Access: | https://doi.org/10.1186/s12951-024-02880-z |
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| author | Huawei Shen Yafei Fu Feifei Liu Wanliang Zhang Yin Yuan Gangyi Yang Mengliu Yang Ling Li |
| author_facet | Huawei Shen Yafei Fu Feifei Liu Wanliang Zhang Yin Yuan Gangyi Yang Mengliu Yang Ling Li |
| author_sort | Huawei Shen |
| collection | DOAJ |
| description | Abstract As the pathophysiological basis of type 2 diabetes mellitus (T2DM), insulin resistance (IR) is closely related to oxidative stress (OS) and inflammation, while nanozymes have a good therapeutic effect on inflammation and OS by scavenging reactive oxygen species (ROS). Hence, AuCePt porous hollow cascade nanozymes (AuCePt PHNs) are designed by integrating the dominant enzymatic activities of three metallic materials, which exhibit superior superoxide dismutase/catalase-like activities, and high drug loading capacity. In vitro experiments proved that AuCePt PHNs can ultra-efficiently scavenge endogenous and exogenous ROS. Moreover, AuCePt PHNs modified with lactobionic acid (LA) and loaded with disulfiram (DSF), named as AuCePt PHNs-LA@DSF, can significantly improve glucose uptake and glycogen synthesis in IR hepatocytes by regulating the insulin signaling pathways (IRS-1/AKT) and gluconeogenesis signaling pathways (FOXO-1/PEPCK). Intravenous administration of AuCePt PHNs-LA@DSF not only showed high liver targeting efficiency, but also reduced body weight and blood glucose and improved IR and lipid accumulation in high-fat diet-induced obese mice and diabetic ob/ob mice. This research elucidates the intrinsic activity of AuCePt PHNs for cascade scavenging of ROS, and reveals the potential effect of AuCePt PHNs-LA@DSF in T2DM treatment. Graphical abstract |
| format | Article |
| id | doaj-art-087bde1201c845b7910e253a5142d196 |
| institution | OA Journals |
| issn | 1477-3155 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | BMC |
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| series | Journal of Nanobiotechnology |
| spelling | doaj-art-087bde1201c845b7910e253a5142d1962025-08-20T02:11:54ZengBMCJournal of Nanobiotechnology1477-31552024-10-0122111910.1186/s12951-024-02880-zAuCePt porous hollow cascade nanozymes targeted delivery of disulfiram for alleviating hepatic insulin resistanceHuawei Shen0Yafei Fu1Feifei Liu2Wanliang Zhang3Yin Yuan4Gangyi Yang5Mengliu Yang6Ling Li7Key Laboratory of Medical Diagnostics of Ministry of Education, Department of Laboratory Medicine, Chongqing Medical UniversityKey Laboratory of Medical Diagnostics of Ministry of Education, Department of Laboratory Medicine, Chongqing Medical UniversityKey Laboratory of Medical Diagnostics of Ministry of Education, Department of Laboratory Medicine, Chongqing Medical UniversityKey Laboratory of Medical Diagnostics of Ministry of Education, Department of Laboratory Medicine, Chongqing Medical UniversityKey Laboratory of Medical Diagnostics of Ministry of Education, Department of Laboratory Medicine, Chongqing Medical UniversityDepartment of Endocrinology, The Second Affiliated Hospital, Chongqing Medical UniversityDepartment of Endocrinology, The Second Affiliated Hospital, Chongqing Medical UniversityKey Laboratory of Medical Diagnostics of Ministry of Education, Department of Laboratory Medicine, Chongqing Medical UniversityAbstract As the pathophysiological basis of type 2 diabetes mellitus (T2DM), insulin resistance (IR) is closely related to oxidative stress (OS) and inflammation, while nanozymes have a good therapeutic effect on inflammation and OS by scavenging reactive oxygen species (ROS). Hence, AuCePt porous hollow cascade nanozymes (AuCePt PHNs) are designed by integrating the dominant enzymatic activities of three metallic materials, which exhibit superior superoxide dismutase/catalase-like activities, and high drug loading capacity. In vitro experiments proved that AuCePt PHNs can ultra-efficiently scavenge endogenous and exogenous ROS. Moreover, AuCePt PHNs modified with lactobionic acid (LA) and loaded with disulfiram (DSF), named as AuCePt PHNs-LA@DSF, can significantly improve glucose uptake and glycogen synthesis in IR hepatocytes by regulating the insulin signaling pathways (IRS-1/AKT) and gluconeogenesis signaling pathways (FOXO-1/PEPCK). Intravenous administration of AuCePt PHNs-LA@DSF not only showed high liver targeting efficiency, but also reduced body weight and blood glucose and improved IR and lipid accumulation in high-fat diet-induced obese mice and diabetic ob/ob mice. This research elucidates the intrinsic activity of AuCePt PHNs for cascade scavenging of ROS, and reveals the potential effect of AuCePt PHNs-LA@DSF in T2DM treatment. Graphical abstracthttps://doi.org/10.1186/s12951-024-02880-zInsulin resistanceOxidative stressNanozymesDisulfiramTargeted drug delivery |
| spellingShingle | Huawei Shen Yafei Fu Feifei Liu Wanliang Zhang Yin Yuan Gangyi Yang Mengliu Yang Ling Li AuCePt porous hollow cascade nanozymes targeted delivery of disulfiram for alleviating hepatic insulin resistance Journal of Nanobiotechnology Insulin resistance Oxidative stress Nanozymes Disulfiram Targeted drug delivery |
| title | AuCePt porous hollow cascade nanozymes targeted delivery of disulfiram for alleviating hepatic insulin resistance |
| title_full | AuCePt porous hollow cascade nanozymes targeted delivery of disulfiram for alleviating hepatic insulin resistance |
| title_fullStr | AuCePt porous hollow cascade nanozymes targeted delivery of disulfiram for alleviating hepatic insulin resistance |
| title_full_unstemmed | AuCePt porous hollow cascade nanozymes targeted delivery of disulfiram for alleviating hepatic insulin resistance |
| title_short | AuCePt porous hollow cascade nanozymes targeted delivery of disulfiram for alleviating hepatic insulin resistance |
| title_sort | aucept porous hollow cascade nanozymes targeted delivery of disulfiram for alleviating hepatic insulin resistance |
| topic | Insulin resistance Oxidative stress Nanozymes Disulfiram Targeted drug delivery |
| url | https://doi.org/10.1186/s12951-024-02880-z |
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