Dual-Regulated Functionalized Liposome–Nanoparticle Hybrids Loaded with Dexamethasone/TGFβ1-siRNA for Targeted Therapy of Glomerulonephritis

Autor: Pengchao Fang, Lu Han, Chunping Liu, Shichen Deng, E. Zhang, Puyang Gong, Yan Ren, Jian Gu, Lili He, Zhi-xiang Yuan
Rok vydání: 2021
Předmět:
Zdroj: ACS Applied Materials & Interfaces. 14:307-323
ISSN: 1944-8252
1944-8244
DOI: 10.1021/acsami.1c20053
Popis: Mesangial cell (MC)-mediated glomerulonephritis is a frequent cause of end-stage renal disease, with immune inflammatory damage and fibrosis as its basic pathological processes. However, the treatment of glomerulonephritis remains challenging owing to limited drug accumulation and serious side effects. Hence, the specific codelivery of "anti-inflammatory/antifibrosis" drugs to the glomerular MC region is expected to yield better therapeutic effects. In this study, liposome-nanoparticle hybrids (Au-LNHy) were formed by coating the surface of gold nanoparticles with a phospholipid bilayer; the Au-LNHys formed were comodified with PEG and α8 integrin antibodies to obtain gold nanoparticle immunoliposomes (Au-ILs). Next, the Au-ILs were loaded with dexamethasone and TGFβ1 siRNA to obtain DXMS/siRNA@Au-ILs. Our results showed that the functionalized nanoparticles had a core-shell structure, a uniform and suitable particle size, low cytotoxicity, and good MC entry, and lysosomal escape abilities. The nanoparticles were found to exhibit enhanced retention in glomerular MCs due to anti-α8 integrin antibody mediation.
Databáze: OpenAIRE