title: Tumor-homing glycol chitosan/polyethylenimine nanoparticles for the systemic delivery of siRNA in tumor-bearing mice.
abstract: Here, we designed a new nano-sized siRNA carrier system composed of biocompatible/biodegradable glycol chitosan polymer (GC) and strongly positively charged polyethylenimine (PEI) polymers. In order to make a stable and tumor-homing nano-sized carrier, each polymer was modified with hydrophobic 5beta-cholanic acid, and they were simply mixed to form self-assembled GC-PEI nanoparticles (GC-PEI NPs), due to the strong hydrophobic interactions of 5beta-cholanic acids in the polymers. The freshly prepared GC-PEI NPs showed a stable nanoparticle structure (350nm) and they presented a strongly positive-charged surface (zeta potential=23.8) that is enough to complex tightly with negatively charged RFP-siRNAs, designed for inhibiting red fluorescent protein (RFP) expression. The siRNA encapsulated nanoparticles (siRNA-GC-PEI NPs) formed more compact and stable nanoparticle structures (250nm) at 1: 5 weight ratio of siRNA to GC-PEI nanoparticles. In vitro RFP expressing B16F10 tumor cell (RFP/B16F10) culture system, the siRNA-GC-PEI NPs presented a rapid time-dependent cellular uptake profile within 1h. Moreover, the internalized siRNA-GC-PEI NPs lead to specific mRNA breaks down. Furthermore, our new formulation of siRNA-GC-PEI NPs presented a significant inhibition of RFP gene expression of RFP/B16F10-bearing mice, due to their higher tumor-targeting ability. These results revealed the promising potential of GC-PEI NPs as a stable and effective nano-sized siRNA delivery system for cancer treatment.
authors.affiliation: Biomedical Research Center, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, South Korea.
authors.forename: Myung Sook
authors.initials: MS
authors.lastname: Huh
authors.forename: Seung-Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Sangjin
authors.initials: S
authors.lastname: Park
authors.forename: Seulki
authors.initials: S
authors.lastname: Lee
authors.forename: Hyunjin
authors.initials: H
authors.lastname: Chung
authors.forename: Sojin
authors.initials: S
authors.lastname: Lee
authors.forename: Yongseok
authors.initials: Y
authors.lastname: Choi
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Oh
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Park
authors.forename: Seo Young
authors.initials: SY
authors.lastname: Jeong
authors.forename: Kuiwon
authors.initials: K
authors.lastname: Choi
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
authors.forename: Ick Chan
authors.initials: IC
authors.lastname: Kwon
mesh_terms: D000818:Animals; D048271:Chitosan; D002793:Cholic Acids; D057927:Hydrophobic and Hydrophilic Interactions; D008164:Luminescent Proteins; D008297:Male; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D011094:Polyethyleneimine / Q000737:chemistry / Q000378:metabolism; D011108:Polymers / Q000737:chemistry* / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D000097573:Red Fluorescent Protein
chemical_list: D048271:Chitosan; D002793:Cholic Acids; D008164:Luminescent Proteins; D011094:Polyethyleneimine; D011108:Polymers; D034741:RNA, Small Interfering; D000097573:Red Fluorescent Protein; C118638:glycol-chitosan; C007036:cholanic acid