Anti-VEGFR2 F(ab′)2 drug conjugate promotes renal accumulation and glomerular repair in diabetic nephropathy

Abstract Poor renal distribution of antibody-based drugs is the key factor contributing to low treatment efficiency for renal diseases and side effects. Here, we prepared F(ab′)2 fragmented vascular endothelial growth factor receptor 2 antibody (anti-VEGFR2 (F(ab′)2) to block VEGFR2 overactivation in diabetic nephropathy (DN). We found that the anti-VEGFR2 F(ab′)2 had a higher accumulation in DN mice kidneys and a comparable VEGFR2 combination with the intact VEGFR2 antibody. Furthermore, we developed an antibody fragment drug conjugate, anti-VEGFR2 F(ab′)2-SS31, comprising anti-VEGFR2 F(ab′)2 fragment linked to the mitochondria-targeted antioxidant peptide SS31. We found that introduce of SS31 potentiated the efficacy of anti-VEGFR2 F(ab′)2. These findings provide proof of concept for the premise that antibody fragment drug conjugate improves renal distribution and merits drug validation in renal disease therapy.