Yhee, Ji Young Lee, So Jin Lee, Sangmin Song, Seungyong Min, Hyun Su Kang, Sun-Woong Son, Sejin Jeong, Seo Young Kwon, Ick Chan Kim, Sun Hwa Kim, Kwangmeyung 2024-01-20T11:04:19Z 2024-01-20T11:04:19Z 2021-09-05 2013-11 1043-1802 https://pubs.kist.re.kr/handle/201004/127497 Transferrin (TF) is widely used as a tumor-targeting ligand for the delivery of anticancer drugs because the TF receptor is overexpressed on the surface of various fast-growing cancer cells. In this article, we report on TF nanoparticles as an siRNA delivery carrier for in vivo tumor-specific gene silencing. To produce siRNA carrying TF nanoparticles (NPs), both TF and siRNA were chemically modified with sulfhydryl groups that can build up self-crosslinked siRNA-TF NPs. Self-polymerized 5'-end thiol-modified siRNA (poly siRNA, psi) and thiolated transferrin (tTF) were spontaneously cross-linked to form stable NPs (psi-tTF NPs) under optimized conditions, and they could be reversibly degraded to release functional monomeric siRNA molecules under reductive conditions. Receptor-mediated endocytosis of TF induced rapid tumor-cell-specific uptake of the psi-tTF NPs, and the internalized NPs resulted in a downregulation of the target protein in red-fluorescent-protein-expressing melanoma cancer cells (RFP/B16F10) with negligible cytotoxicity. After systemic administration, the psi-tTF NPs showed marked accumulation at the tumor, leading to successful target-gene silencing in vivo. This psi-tTF NP system provided a safe and effective strategy for in vivo systemic siRNA delivery for cancer therapy. English AMER CHEMICAL SOC RNA INTERFERENCE CATIONIC LIPIDS CELLULAR UPTAKE EFFICIENT RECEPTOR MECHANISM PROTEINS CELLS DNA Tumor-Targeting Transferrin Nanoparticles for Systemic Polymerized siRNA Delivery in Tumor-Bearing Mice Article 10.1021/bc400226b 1 BIOCONJUGATE CHEMISTRY, v.24, no.11, pp.1850 - 1860 BIOCONJUGATE CHEMISTRY 24 11 1850 1860 scie scopus 000327413100011 2-s2.0-84888586255 Biochemical Research Methods Biochemistry & Molecular Biology Chemistry, Multidisciplinary Chemistry, Organic Biochemistry & Molecular Biology Chemistry Article RNA INTERFERENCE CATIONIC LIPIDS CELLULAR UPTAKE EFFICIENT RECEPTOR MECHANISM PROTEINS CELLS DNA