title: Biodegradable nanoparticles composed of dendrigraft poly-L-lysine for gene delivery.
abstract: We developed novel gene vectors composed of dendrigraft poly-L-lysine (DGL). The transgene expression efficiency of the pDNA/DGL complexes (DGL complexes) was markedly higher than that of the control pDNA/poly-L-lysine complex. However, the DGL complexes caused cytotoxicity and erythrocyte agglutination at high doses. Therefore, γ-polyglutamic acid (γ-PGA), which is a biodegradable anionic polymer, was added to the DGL complexes to decrease their toxicity. The resultant ternary complexes (DGL/γ-PGA complexes) were shown to be stable nanoparticles, and those with γ-PGA to pDNA charge ratios of >8 had anionic surface charges. The transgene expression efficiency of the DGL/γ-PGA complexes was similar to that of the DGL complexes; however, they exhibited lower cytotoxicity and did not induce erythrocyte agglutination at high doses. After being intravenously administered to mice, the DGL6 complex demonstrated high transfection efficiency in the liver, lungs, and spleen, whereas the DGL6/γ-PGA8 complex only displayed high transfection efficiency in the spleen. Future studies should examine the utility of DGL and DGL/γ-PGA complexes for clinical gene therapy.
authors.affiliation: Department of Hospital Pharmacy, Nagasaki University Hospital, Nagasaki, Japan.
authors.forename: Yukinobu
authors.initials: Y
authors.lastname: Kodama
authors.affiliation: Department of Hospital Pharmacy, Nagasaki University Hospital, Nagasaki, Japan.
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Hospital Pharmacy, Nagasaki University Hospital, Nagasaki, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kurosaki
authors.affiliation: Department of Hospital Pharmacy, Nagasaki University Hospital, Nagasaki, Japan.
authors.forename: Kanoko
authors.initials: K
authors.lastname: Egashira
authors.affiliation: Department of Hospital Pharmacy, Nagasaki University Hospital, Nagasaki, Japan.
authors.forename: Toyoharu
authors.initials: T
authors.lastname: Mine
authors.affiliation: Department of Hospital Pharmacy, Nagasaki University Hospital, Nagasaki, Japan.
authors.forename: Hiroo
authors.initials: H
authors.lastname: Nakagawa
authors.affiliation: Department of Hospital Pharmacy, Nagasaki University Hospital, Nagasaki, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Muro
authors.affiliation: Department of Hospital Pharmacy, Nagasaki University Hospital, Nagasaki, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kitahara
authors.affiliation: Department of Hospital Pharmacy, Nagasaki University Hospital, Nagasaki, Japan.
authors.forename: Norihide
authors.initials: N
authors.lastname: Higuchi
authors.affiliation: Department of Hospital Pharmacy, Nagasaki University Hospital, Nagasaki, Japan. Electronic address: sasaki@nagasaki-u.ac.jp.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D000838:Anions / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D004247:DNA / Q000235:genetics; D004912:Erythrocytes; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics; D008239:Lysine / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000235:genetics; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D011099:Polyglutamic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D011107:Polylysine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry; D014162:Transfection / Q000379:methods
chemical_list: D000838:Anions; D011108:Polymers; C511775:poly(gamma-glutamic acid); D011107:Polylysine; D011099:Polyglutamic Acid; C030391:poly(glutamic acid-lysine); D004247:DNA; D008239:Lysine
keywords: Biodegradable; Dendrigraft poly-l-lysine; Gene delivery; Nanoparticle; Ternary complex; γ-Polyglutamic acid