title: A novel potential biocompatible hyperbranched polyspermine for efficient lung cancer gene therapy.
abstract: The clinical successful application of gene therapy critically depends upon the development of non-toxic and efficient delivery system. Although polycationic non-viral vectors hold great promise in nanomedicine, the exploring of application in clinics still remains a big challenge. To develop a non-toxic and efficient non-viral gene delivery system, two kinds of endogenous substance, citric acid (CA) and spermine (SPE), were used to prepare a new low charge density hyperbranched polyspermine (HPSPE) by one-pot polymerization. The biocompatibility evaluated by hemolytic activity and red blood cell (RBC) aggregation indicated that HPSPE was highly biocompatible without causing hemolysis and RBC aggregation compared with PEI as well as SPE. The MTS assay also demonstrated that the cell viability of HPSPE was above 90% even at 200 μg/mL at different time (24 and 72 h), which much higher than PEI 25K. Besides, HPSPE showed high transfection efficiency without any toxic effect after aerosol delivery to the mice. Moreover, aerosol delivery of HPSPE/Akt1 shRNA significantly reduced tumor size and numbers and efficiently suppressed lung tumorigenesis ultimately in K-ras(LA1) lung cancer model mice. These results suggest that low charge density as well as endogenous substance skeleton endow HPSPE with great potential for toxicity-free and efficient gene therapy.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
authors.forename: Rong-Lin
authors.initials: RL
authors.lastname: Xie
authors.affiliation: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Yoon-Jeong
authors.initials: YJ
authors.lastname: Jang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xing
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
authors.forename: Bing-Feng
authors.initials: BF
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
authors.forename: Feng-Zhen
authors.initials: FZ
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Cui
authors.affiliation: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, South Korea; Graduate School of Convergence Science and Technology, Seoul National University, Suwon 443-270, South Korea; Graduate Group of Tumor Biology, Seoul National University, Seoul 151-742, South Korea; Advanced Institute of Convergence Technology, Seoul National University, Suwon 443-270, South Korea. Electronic address: mchotox@snu.ac.kr.
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, People's Republic of China. Electronic address: jianghulin3@gmail.com.
authors.forename: Hu-Lin
authors.initials: HL
authors.lastname: Jiang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019343:Citric Acid / Q000737:chemistry; D004247:DNA / Q000008:administration & dosage*; D004912:Erythrocytes / Q000187:drug effects / Q000473:pathology; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008297:Male; D008810:Mice, Inbred C57BL; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D051381:Rats; D013096:Spermine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins; D019343:Citric Acid; D013096:Spermine; D004247:DNA; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt
keywords: Aerosol delivery; Biocompatibility; Citric acid; Citric acid (PubChem CID: 311); Fluorescein isothiocyanate (PubChem CID: 18730); Hyperbranched polyspermine; Lung cancer; Pyridine (PubChem CID: 1049); Spermine (PubChem CID: 1103); Triphenyl phosphate (PubChem CID: 7540)