Lee, Jinju Ahn, Hyung Jun 2024-01-19T22:00:33Z 2024-01-19T22:00:33Z 2021-09-03 2018-09-10 0006-291X https://pubs.kist.re.kr/handle/201004/120918 Although siRNA-mediated downregulation technology has been highly successful in suppressing the expression of any disease-related gene, systemic delivery of siRNA for the clinical applications remains challenging, especially in the use of cancer therapy. DC-Chol/DOPE cationic liposomes as one of the most attractive vehicles for gene delivery have been widely exploited for transfection of siRNA into cells, but complexity of systemic delivery has allowed only their direct injection into local targets due to the formation of aggregations with negatively-charged blood components. Herein, we demonstrate the effects of PEGylation on DC-Chol/DOPE cationic liposomes for systemic siRNA delivery in cancer therapy. In contrast to non-PEGylated DC-Chol/DOPE-siRNA lipoplexes, PEGylated DC-Chol/DOPE-SiRNA lipoplexes reduce the excretion by kidneys and scavenging in liver, prolonging the circulation time in vivo, and ultimately increase their preferential tumor accumulation. Therefore, systemic injection of PEGylated DC-Chol/DOPE liposomes loaded with siRNA against kinesin spindle protein (KSP) gene exhibited a high level of target gene silencing at tumor sites and substantial suppression of tumor growth. Furthermore, systemically administered PEGylated lipoplexes did not lead to any activation of innate immune responses in the immunocompetent mice. These results suggest the potential of PEGylated DC-Chol/DOPE liposomes as a systemic delivery carrier for siRNA-mediated cancer therapy. (C) 2018 Elsevier Inc. All rights reserved. English ACADEMIC PRESS INC ELSEVIER SCIENCE GENE DELIVERY TRANSFECTION EFFICIENCY TOXICITY EXPRESSION INHIBITOR MELANOMA CELLS PEGylated DC-Chol/DOPE cationic liposomes containing KSP siRNA as a systemic siRNA delivery Carrier for ovarian cancer therapy Article 10.1016/j.bbrc.2018.07.104 1 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.503, no.3, pp.1716 - 1722 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 503 3 1716 1722 scie scopus 000444222100080 2-s2.0-85050268984 Biochemistry & Molecular Biology Biophysics Biochemistry & Molecular Biology Biophysics Article GENE DELIVERY TRANSFECTION EFFICIENCY TOXICITY EXPRESSION INHIBITOR MELANOMA CELLS Cationic liposome siRNA RNAi Systemic delivery Cancer therapy