Natural ursolic acid based self-therapeutic polymer as nanocarrier to deliver natural resveratrol for natural therapy of acute kidney injury

Journal of Nanobiotechnology
Yuanpeng Nie1, Liying Wang2, Shengbo Liu3, Chenyang Dai4, Tianjiao Cui1, Yan Liu1, Xinru You5, Xiaohua Wang1, Jun Wu2,4,6,7, Zhihua Zheng1
1Department of Nephrology, Center of Kidney and Urology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
2Department of Hematology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China
3Department of Thoracic Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
4School of Biomedical Engineering, Sun Yat-sen University, Shenzhen, China
5Center for Nanomedicine and Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA
6Bioscience and Biomedical Engineering Thrust, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou, China
7Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong SAR, China

Tóm tắt

AbstractAcute kidney injury (AKI) is a common kidney disease associated with excessive reactive oxygen species (ROS). Unfortunately, due to the low kidney targeting and undesired side effects, the existing antioxidant and anti-inflammatory drugs are unavailable for AKI management in clinic. Therefore, it’s essential to develop effective nanodrugs with high renal targeting and biocompatibility for AKI treatment. Herein, we reported a novel nanodrug for AKI treatment, utilizing poly(ursolic acid) (PUA) as a bioactive nanocarrier and resveratrol (RES) as a model drug. The PUA polymer was synthesized form ursolic acid with intrinsic antioxidant and anti-inflammatory activities, and successfully encapsulated RES through a nanoprecipitation method. Subsequently, we systemically investigated the therapeutic potential of RES-loaded PUA nanoparticles (PUA NPs@RES) against AKI. In vitro results demonstrated that PUA NPs@RES effectively scavenged ROS and provided substantial protection against H2O2-induced cellular damage. In vivo studies revealed that PUA NPs significantly improved drug accumulation in the kidneys and exhibited favorable biocompatibility. Furthermore, PUA NPs alone exhibited additional anti-inflammatory and antioxidant effect, synergistically enhancing therapeutic efficacy in AKI mouse models when combined with RES. Overall, our study successfully developed an effective nanodrug using self-therapeutic nanocarriers, presenting a promising option for the treatment of AKI. Graphical abstract

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