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논문분류	춘계학술대회 초록집
제목	Targeted Anti-IL-1beta Bacteroides fragilis Outer Membrane Vesicles Alleviate Inflammatory Injury in Diabetic Nephropathy
저자	Liang Li
출판정보	2024; 2024(1):
키워드
초록	Objectives: This study aimed to construct renal-targeted Bacteroides fragilis outer membrane vesicles (OMVs) loaded with interleukin-1β (IL-1β) single-chain variable fragments (scFv) of for the treatment of diabetic nephropathy (DN). These OMVs derived from human commensal non-toxigenic Bacteroides fragilis have been proven to play an immunosuppressive role in the intestine and distant organs. This targeted drug delivery platform built with this as a carrier is expected to relieve kidney inflammation in the development of DN. Methods: We recombinantly expressed the scFv based on the Gevokizumab sequence in Escherichia coli, and loaded it into the OMVs derived from Bacteroides fragilis. The targeting peptide was connected to the membrane surface through a copper-free catalyzed click chemistry reaction. The package, which consisted of OMVs and the scFv targeting IL-1β in the kidney (OMV-KTP-scFv) was obtained. OMV-KTP-scFv intervened in HK-2 cells and healthy mice respectively, and evaluated its in vitro and in vivo drug safety. The concentration of IL-1β scFv in blood and kidney tissues at different time points were measured using streptozotocin (STZ)-induced diabetic mice. In vitro, OMV-KTP-scFv was used to prevent inflammation in mouse primary renal tubular epithelial cells induced by high glucose, and in vivo to alleviate kidney injury in STZ-induced diabetic mice. Results: The prepared OMV-KTP-scFv had high stability, effectively extended the plasma half-life of scFv, and could deliver scFv accurately to the proximal renal tubules. Furthermore, OMV-KTP-scFv also had good safety in vitro and in vivo, and no obvious biotoxicity was found during long-term in vivo administration. In addition, our results show that OMV-KTP-scFv significantly alleviated renal tubular injury. Conclusions: Our findings demonstrated that OMVs of Bacteroides fragilis targeting the kidney can deliver the IL-1β scFv to the renal tubulointerstitium and reduce the renal interstitial injury in DN by antagonizing local inflammation.
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