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. 2021 Dec 12;15(4):3556–3568. doi: 10.1007/s12274-021-3894-x

Targeted delivery of celastrol to glomerular endothelium and podocytes for chronic kidney disease treatment

Qingsi Wu 1,3, Jiading Wang 2,3, Yuanfang Wang 1,3, Ling Xiang 1,3, Yulu Tan 1,3, Jiaxing Feng 1,3, Zhirong Zhang 1,3,✉, Ling Zhang 2,3,✉
PMCID: PMC8666268  PMID: 34925707

Abstract

The etiology of chronic kidney disease (CKD) is complex and diverse, which could be briefly categorized to glomerular- or tubular-originated. However, the final outcomes of CKD are mainly glomerular sclerosis, endothelial dysfunction and injury, and chronic inflammation. Thus, targeted delivery of drugs to the glomeruli in order to ameliorate glomerular endothelial damage may help alleviate CKD and help enrich our knowledge. The herb tripterygium wilfordii shows therapeutic effect on kidney disease, and celastrol (CLT) is one of its active ingredients but with strong toxicity. Therefore, based on the unique structure and pathological characteristics of the glomerulus, we designed a targeted delivery system named peptides coupled CLT-phospholipid lipid nanoparticles (PC-PLNs) to efficiently deliver CLT to damaged endothelial cells and podocytes in the glomerulus for CKD treatment and research. PC-PLNs could effectively inhibit inflammation, reduce endothelial damage, alleviate CKD severity, and reduce the toxicity of CLT. We also studied the mechanism of CLT in the treatment of nephropathy and found that CLT can increase the level of NO by increasing eNOS while inhibiting the expression of VCAM-1, thus provides an anti-inflammatory effect. Therefore, our study not only offered an efficient CKD drug formulation for further development, but also provided new medical knowledge about CKD.

graphic file with name 12274_2021_3894_Fig1_HTML.jpg

Electronic Supplementary Material

Supplementary material (attached with all the supporting tables and figures mentioned in this work) is available in the online version of this article at 10.1007/s12274-021-3894-x.

Keywords: celastrol, chronic kidney disease (CKD), glomerulus, endothelial cells, VCAM-1

Electronic Supplementary Material

12274_2021_3894_MOESM1_ESM.pdf (1.1MB, pdf)

Targeted delivery of celastrol to glomerular endothelium and podocytes for chronic kidney disease treatment

Acknowledgements

This work was supported by the Regional Innovation and Development Joint Fund (No. U20A20411) and the National Science Fund for Excellent Young Scholars (No. 82022070).

Contributor Information

Zhirong Zhang, Email: zrzzl@vip.sina.com.

Ling Zhang, Email: zhangling83@scu.edu.cn.

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12274_2021_3894_MOESM1_ESM.pdf (1.1MB, pdf)

Targeted delivery of celastrol to glomerular endothelium and podocytes for chronic kidney disease treatment

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