title: Suppression of tumor growth in lung cancer xenograft model mice by poly(sorbitol-co-PEI)-mediated delivery of osteopontin siRNA.
abstract: Small interfering RNA (siRNA)-mediated gene silencing represents a promising strategy for treating diseases such as cancer; however, specific gene silencing requires an effective delivery system to overcome the instability and low transfection efficiency of siRNAs. To address this issue, a polysorbitol-based transporter (PSOT) was prepared by low molecular weight branched polyethylenimine (bPEI) crosslinked with sorbitol diacrylate (SDA). Osteopontin (OPN) gene, which is highly associated with non-small cell lung cancer (NSCLC) was targeted by siRNA therapy using siRNA targeting OPN (siOPN). Characterization study confirmed that PSOT formed compact complexes with siOPN and protected siOPN against degradation by RNase. PSOT/siOPN complexes demonstrated low cytotoxicity and enhanced transfection efficiency in vitro, suggesting that this carrier may be suitable for gene silencing. In the A549 and H460 lung cancer cell lines, PSOT/siOPN complexes demonstrated significant silencing efficiency at both RNA and protein levels. To study in vivo tumor growth suppression, two lung cancer cell-xenograft mouse models were prepared and PSOT/siOPN complexes were delivered into the mice through intravenous injection. The siOPN-treated groups demonstrated significantly reduced OPN expression at both the RNA and protein levels as well as suppression of tumor volume and weight. Taken together, siOPN delivery using PSOT may present an effective and novel therapeutic system for lung cancer treatment.
authors.affiliation: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea; Graduate Group of Tumor Biology, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Won-Young
authors.initials: WY
authors.lastname: Cho
authors.affiliation: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Hong
authors.affiliation: Department of Agricultural Biotechnology & Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: Bijay
authors.initials: B
authors.lastname: Singh
authors.affiliation: Department of Agricultural Biotechnology & Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea; Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Harvard Medical School, Boston, MA 02115, United States; Laboratory for Nanoengineering & Drug Delivery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States.
authors.forename: Mohammad Ariful
authors.initials: MA
authors.lastname: Islam
authors.affiliation: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea; Graduate Group of Tumor Biology, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Somin
authors.initials: S
authors.lastname: Lee
authors.affiliation: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Ah Young
authors.initials: AY
authors.lastname: Lee
authors.affiliation: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Nomundelger
authors.initials: N
authors.lastname: Gankhuyag
authors.affiliation: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Kyeong-Nam
authors.initials: KN
authors.lastname: Yu
authors.affiliation: Croen Research, Suwon 443-733, Republic of Korea.
authors.forename: Kwang-Ho
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Croen Research, Suwon 443-733, Republic of Korea.
authors.forename: Young-Chan
authors.initials: YC
authors.lastname: Park
authors.affiliation: Department of Agricultural Biotechnology & Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea. Electronic address: chocs@snu.ac.kr.
authors.forename: Chong-Su
authors.initials: CS
authors.lastname: Cho
authors.affiliation: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea; Graduate Group of Tumor Biology, Seoul National University, Seoul 151-742, Republic of Korea; Graduate School of Convergence Science and Technology, Seoul National University, Suwon, Republic of Korea; Advanced Institute of Convergence Technology, Seoul National University, Suwon 443-270, Republic of Korea; Institute of GreenBio Science Technology, Seoul National University, Pyeongchang-gun, Gangwon-do, Republic of Korea. Electronic address: mchotox@snu.ac.kr.
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry*; D015870:Gene Expression; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053495:Osteopontin / Q000235:genetics*; D011094:Polyethyleneimine / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D013012:Sorbitol / Q000737:chemistry*; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D004337:Drug Carriers; D034741:RNA, Small Interfering; C506896:Spp1 protein, mouse; D053495:Osteopontin; D013012:Sorbitol; D011094:Polyethyleneimine
keywords: Lung cancer gene therapy; Osteopontin; Polysorbitol-based transporter; siRNA