Targeting Interstitial Myofibroblast-Expressed Integrin αvβ3 Alleviates Renal Fibrosis

• DOI: 10.1021/acs.molpharmaceut.0c01182
• Publication Date: 2021-02-06T16:40:15Z
• Authors: Jian Zhou; Rui Li; Jinhang Zhang; Qinhui Liu; Tong Wu; Qin Tang; Cuiyuan Huang; Zijing Zhang; Ya Huang; Hui Huang; Guorong Zhang; Yingnan Zhao; Ting Zhang; Li Mo; Yanping Li; Jinhan He
• Keywords: Myofibroblast; Celastrol

Renal fibrosis is the final manifestation of various chronic kidney diseases. Interstitial myofibroblasts, which are reported to highly express integrin αvβ3, effector cells in renal fibrogenesis. Since current therapies do not efficiently target these cells, there no effective therapeutic method for preventing or mitigating disease. Here, we modified sterically stable PEGylated liposomes with pentapeptide cRGDfC (RGD-Lip), has a high affinity specifically deliver drug interstitial myofibroblasts. Our results showed that attaching significantly increased their uptake by activated fibroblasts NRK-49F and this effect was greatly abolished adding excess-free knockdown αvβ3. Systemic administration RGD-Lip gave rise significant accumulation fibrotic kidney, ascribed specific recognition αvβ3 on When loaded celastrol, RGD-guided dramatically depressed proliferation activation vitro. Additionally, celastrol-loaded markedly attenuated fibrosis, injury, inflammation induced unilateral ureteral obstruction (UUO) mice, without inducing systemic toxicity. Thus, liposomal system shows great promise delivering agents myofibroblasts treatment minimal side effects.