Efficacy of internalized RGD-modified echogenic liposomes in diagnosis and treatment in a mouse model of rheumatoid arthritis
GAN Zhen
WU Hao
WU Haohan
ZHOU Meijun
YAN Fei
LIU Hongmei
Abstract：Objective To prepare internalized RGD (iRGD)-modified echogenic liposomes containing methotrexate (MTX) and indocyanine green (ICG) (iRGD-MTX-ICG-ELIP) and evaluate its targeting efficiency and inhibitory effect combined with ultrasound on synovial cells. Methods iRGD-MTX-ICG-ELIP was prepared by the thin-film rehydration and freeze-lyophilization method and its general characteristics and acoustic responsiveness were assessed. The targeting effect of the prepared liposome was observed by assessing its cell uptake in vitro.In a mouse model of rheumatiod arthritis,the targeting effect of the prepared liposome was determined by detecting the fluorescence intensity of the drug in arthrosis.The inhibitory effect of iRGD-MTX-ICG-ELIP combined with ultrasound on synovial MH7A cells in vitro were investigated using CCK8 test. Results The average diameter and zeta potential of iRGD-MTX-ICG-ELIP was 134.4 ± 17.61 nm and-10.07 ± 4.28 mV, and the entrapment efficiency of MTX and ICG was (62.56 ± 0.77)% and (95.13 ± 0.82)%, respectively. With ultrasound exposure, the release of MTX and ICG from iRGD-MTX-ICG-ELIP increased with the ultrasound intensity and with the exposure time. In HUVECs, the uptake efficiency of iRGD-MTX-ICG-ELIP was 1.89 times higher than that of non-targeted MTX-ICG-ELIP(P<0.05).In vivo imaging of mouse joint with rheumatiod arthritis showed that the fluorescence intensity of iRGD-MTX-ICG-ELIP was significantly stronger than that of the non-targeted liposome. CCK8 assay showed that iRGD-MTX-ICG-ELIP combined with ultrasound resulted in a survival rate of MH7A cells of (32.49±3.04)%, significantly lower than the rate of cells treated with iRGD-MTX-ICG-ELIP but without ultrasound(P<0.05).Conclusions iRGD-MTX-ICG-ELIP has a suitable particle size and can effectively target HUVECs and the joints with rheumatiod arthritis. With a good drug entrapment efficiency and acoustic responsiveness, the drug-loaded liposome shows enhanced inhibitory effect on MH7A cells combined with ultrasound in vitro, suggesting its potential in the treatment of rheumatoid arthritis.
Keywords：targeted drug deliveryechogenic liposomesultrasound triggered releaserheumatoid arthritis
Publication Date：2017-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：7( 1283-1289 )