Choi, Kyung-mi Jang, Mihue Kim, Jong Hwan Ahn, Hyung Jun 2024-01-20T09:04:23Z 2024-01-20T09:04:23Z 2021-09-05 2014-08 0142-9612 https://pubs.kist.re.kr/handle/201004/126512 Anticancer therapeutics delivering exogenous siRNA have been explored to suppress the tumor-associated genes, but several limitations of siRNA delivery such as tumor-targeted delivery, controlled siRNA release at the sites of interest, or instabilities of siRNA in physiological fluids should be preferentially addressed for its clinical applications. As an attempt to meet these criteria, we designed a supramolecular assembly, which was composed of cholesterol-bearing hyaluronic acid (HA-Chol) conjugates and 2b RNA-binding protein (2b)/siRNA complexes. In contrast to the traditional siRNA polyplexes using electrostatic interactions, HA-Chol nanoparticles, as a results of self-assembly of HA-Chol conjugates, provide the hydrophobic core that acts as the container for 2b protein/siRNA complexes, where a high affinity of 2b protein for siRNA could neutralize the negative-charged siRNA. Here, we investigated the potential of HA-Chol/2b/siRNA complexes as the siRNA carriers that provide encapsulation, protection, and targeted delivery of siRNA. The HA-Chol nanoparticles could selectively deliver 2b protein/siRNA complexes to the tumor cells with up-regulated CD44 receptors and suppress the expression of target gene. The pH-associated binding properties of siRNA for 2b proteins allowed the controlled release of siRNA in the endocytic compartments, and ultimately the released siRNA could obtain the RNAi acitivities in the cells, whereas the encapsulated 2b proteins still stayed within the HA-Chol nanoparticles. Our delivery systems demonstrate the promising potential of the efficient siRNA carriers in the anticancer therapeutic applications. (C) 2014 Elsevier Ltd. All rights reserved. English ELSEVIER SCI LTD CHIMERIC CAPSID PROTEIN IN-VIVO GENE DELIVERY HYDROPHOBIZED POLYSACCHARIDE ANTIVIRAL IMMUNITY ANTITUMOR-ACTIVITY CELLS THERAPEUTICS EFFICIENT INTERFERENCE Tumor-specific delivery of siRNA using supramolecular assembly of hyaluronic acid nanoparticles and 2b RNA-binding protein/siRNA complexes Article 10.1016/j.biomaterials.2014.04.096 1 BIOMATERIALS, v.35, no.25, pp.7121 - 7132 BIOMATERIALS 35 25 7121 7132 scie scopus 000338386800043 2-s2.0-84902117695 Engineering, Biomedical Materials Science, Biomaterials Engineering Materials Science Article CHIMERIC CAPSID PROTEIN IN-VIVO GENE DELIVERY HYDROPHOBIZED POLYSACCHARIDE ANTIVIRAL IMMUNITY ANTITUMOR-ACTIVITY CELLS THERAPEUTICS EFFICIENT INTERFERENCE siRNA siRNA carrier Supramolecular assembly Hyaluronic acid-choleresterol conjugate