Jump to main content
Jump to site search

E-selectin-targeting, inflammatory microenvironment-responsive dextran-curcumin polymeric prodrug for acute kidney injury


Based on the overproduction of matrix metalloproteinase-2 (MMP-2) in renal tissue during acute kidney injury (AKI) occurrence, we developed a MMP-2 enzyme-triggered polymeric prodrug with sialic acid (SA) as targeting group to the inflamed vascular endothelial cells for enhanced therapeutic outcomes. The MMP-2-responsove peptide, PVGLIG, was used to afford the polymeric prodrug the ability to rapidly release anti-inflammatory drug, curcumin (CUR), after the targeted site has been reached and improve drug concentration in target tissue. The sialic acid-dextran-PVGLIG-curcumin (SA-DEX-PVGLIG-CUR) polymeric prodrug was successfully synthesized via multi-step chemical reactions and characterized by 1H NMR. The water solubility of CUR was significantly increased in polymeric prodrug and approximately 23-fold higher than that of free CUR. In vitro drug release results showed that the release rate of SA-DEX-PVGLIG-CUR was significantly enhanced than that of SA-DEX-CUR in dissolve medium containing MMP-2 enzyme, suggesting SA-DEX-PVGLIG-CUR had rapid drug release characteristics under inflammatory environment. Cellular uptake test confirmed that SA-DEX-PVGLIG-CUR was effectively internalized by inflamed vascular endothelial cells in comparison to that by normal cells, and the mechanism was associated with the specific interaction between SA and E-selectin receptors specifically expressed on inflamed vascular endothelial cells. Bio-distribution results further demonstrated the rapid and increased renal accumulation of SA-DEX-PVGLIG-CUR in AKI mice. Benefiting from rapid drug release in renal tissue, SA-DEX-PVGLIG-CUR effectively ameliorated pathological progression of AKI compared with free CUR and SA-DEX-CUR, as reflected by the improved renal functions, histopathological changes, pro-inflammatory cytokines, oxidative stress and expression of apoptotic related proteins. Taken together, this study provided a new therapeutic strategy for the treatment of AKI.

Back to tab navigation

Supplementary files

Publication details

The article was received on 17 Jul 2018, accepted on 07 Oct 2018 and first published on 09 Oct 2018

Article type: Paper
DOI: 10.1039/C8BM00813B
Citation: Biomater. Sci., 2018, Accepted Manuscript
  •   Request permissions

    E-selectin-targeting, inflammatory microenvironment-responsive dextran-curcumin polymeric prodrug for acute kidney injury

    J. Hu, D. Liu, J. Qi, K. Lu, F. Jin, X. Ying, J. You and Y. Du, Biomater. Sci., 2018, Accepted Manuscript , DOI: 10.1039/C8BM00813B

Search articles by author