Effect of PEG anchor in PEGylation of folate-modified cationic liposomes with PEG-derivatives on systemic siRNA delivery into the Tumor. (2nd January 2023)

• Record Type: Journal Article
• Authors: Tang, Min; Sakasai, Sho; Onishi, Hiraku; Kawano, Kumi; Hattori, Yoshiyuki
• Is Part Of: Journal of drug targeting. Volume 31:Number 1(2023)
• Page Start: 74
• Page End: 88
• Publication Date: 2023-01-02
• Subjects: Cationic liposome -- PEGylation -- folate -- folate receptor -- siRNA delivery -- gene knock-down; Drug delivery systems -- Periodicals; Drug Delivery Systems; Vehicles; Drug Administration Routes; Drug Evaluation; 615.7
• DOI: 10.1080/1061186X.2022.2104860
• Languages: English
• ISSNs: 1061-186X

Abstract

Abstract: In this study, we prepared small interfering RNA (siRNA)/cationic liposome complexes (lipoplexes) modified with folate (FA)-polyethylene glycol (PEG, MW 2000, 3400 or 5000)-1, 2-distearoyl- sn -glycero-3-phosphoethanolamine (DSPE) to facilitate their uptake into tumor cells via folate receptor (FR), and with PEG1600 -cholesterol (PEG1600 -Chol) or PEG2000 -chondroitin sulfate conjugate (PEG2000 -CS), to enhance their systemic stability. Among the FA-PEG-modified siRNA lipoplexes, 0.5 mol% FA-PEG5000 -DSPE-modified lipoplexes with 2.5 mol% PEG2000 -CS or PEG1600 -Chol (LP-0.5F5 /2.5P2 -CS and LP-0.5F5 /2.5P1.6 -CL, respectively) exhibited selective growth inhibition of human nasopharyngeal carcinoma KB cells through transduction with polo-like kinase 1 (PLK1) siRNA. Furthermore, the LP-0.5F5 /2.5P2 -CS and LP-0.5F5 /2.5P1.6 -CL lipoplexes exhibited decreased agglutination with erythrocytes through PEGylation, and markedly decreased the accumulation of siRNA in murine lungs after systemic injection. Finally, systemic injection of LP-0.5F5 /2.5P2 -CS and LP-0.5F5 /2.5P1.6 -CL lipoplexes resulted in accumulation of siRNA in KB tumor xenografts. These findings suggest that PEGylation of FA-PEG5000 -DSPE-modified siRNA lipoplexes with PEG2000 -CS or PEG1600 -Chol might improve their systemic stability without the loss of selective transfection activity in tumor cells.