Unique features of a pH-sensitive fusogenic peptide that improves the transfection efficiency of cationic liposomes

Futaki, Shiroh; Masui, Yumi; Nakase, Ikuhiko; Sugiura, Yukio; Nakamura, Takashi; Kogure, Kentaro; Harashima, Hideyoshi

doi:10.1002/jgm.796

Cited by 67 publications

(53 citation statements)

References 15 publications

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“…These polymers, however, are of limited use due to their cytotoxicity (18). Instead, nontoxic lysogenic peptides, such as Glu-Ala-Leu-Ala (GALA) (19,20) derived from certain viruses or bacteria, are used for endosome escape of micelles and liposomes (21) or are covalently bound to nanoconjugates to deliver water-soluble proteins, antibodies, and nucleic acids (9,22).…”

Section: Inhibition Of Brain Tumor Growth By Intravenous Poly (β-L-mamentioning

confidence: 99%

Inhibition of brain tumor growth by intravenous poly(β- l -malic acid) nanobioconjugate with pH-dependent drug release

Inoue

Ljubimov

Patil

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

160

180

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Effective treatment of brain neurological disorders such as Alzheimer's disease, multiple sclerosis, or tumors should be possible with drug delivery through blood–brain barrier (BBB) or blood–brain tumor barrier (BTB) and targeting specific types of brain cells with drug release into the cell cytoplasm. A polymeric nanobioconjugate drug based on biodegradable, nontoxic, and nonimmunogenic polymalic acid as a universal delivery nanoplatform was used for design and synthesis of nanomedicine drug for i.v. treatment of brain tumors. The polymeric drug passes through the BTB and tumor cell membrane using tandem monoclonal antibodies targeting the BTB and tumor cells. The next step for polymeric drug action was inhibition of tumor angiogenesis by specifically blocking the synthesis of a tumor neovascular trimer protein, laminin-411, by attached antisense oligonucleotides (AONs). The AONs were released into the target cell cytoplasm via pH-activated trileucine, an endosomal escape moiety. Drug delivery to the brain tumor and the release mechanism were both studied for this nanobiopolymer. Introduction of a trileucine endosome escape unit resulted in significantly increased AON delivery to tumor cells, inhibition of laminin-411 synthesis in vitro and in vivo, specific accumulation in brain tumors, and suppression of intracranial glioma growth compared with pH-independent leucine ester. The availability of a systemically active polymeric drug delivery system that passes through the BTB, targets tumor cells, and inhibits glioma growth gives hope for a successful strategy of glioma treatment. This delivery system with drug release into the brain-specific cell type could be useful for treatment of various brain pathologies.

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Section: Inhibition Of Brain Tumor Growth By Intravenous Poly (β-L-mamentioning

confidence: 99%

Inhibition of brain tumor growth by intravenous poly(β- l -malic acid) nanobioconjugate with pH-dependent drug release

Inoue

Ljubimov

Patil

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

160

180

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“…1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) was purchased from AVANTI Polar Lipids Inc. (Alabaster, AL, USA). Stearyl octaarginine (STR-R8) [6,17] and cholesteryl GALA peptide (Cho-GALA) [15,16] was obtained from Kurabo Industries, Ltd. (Osaka, Japan). Protamine was purchased from CALBIO CHEM (Darmstadt, Germany).…”

Section: Methodsmentioning

confidence: 99%

“…HA is a natural ligand for cancer cells and liver endothelial cells overexpressing CD44, thus it would be expected that HA would be a specific ligand for / targeted to cancer and liver endothelial cells. In that study, we investigated the transgene expression of an R8-MEND modified with HA in liver endothelial cells (liver ECs) (CD44 positive cells), and determined the optimal composition of MEND needed for efficient transgene expression in liver ECs, which possesses an HA-coated lipid envelope modified with the R8 [6,7] and GALA, a pH-sensitive fusogenic peptide for efficient endosomal escape [15,16] (HA-R8/GALA-MEND). 6 The focus of this study was on the mechanism responsible for the cellular uptake pathway and transgene expression of the HA-R8/GALA-MEND.…”

Section: Introductionmentioning

confidence: 99%

Hyaluronic acid controls the uptake pathway and intracellular trafficking of an octaarginine-modified gene vector in CD44 positive- and CD44 negative-cells

2015

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“…It can therefore be concluded that the S2 peptide represents a safer targeting moiety than R8 for mitochondrial delivery. comprised of a cellular uptake moiety (R8) and an endosomal escape moiety (GALA) constructed by the multi-layering method (Akita et al, 2009;Akita et al, 2011;El-Sayed et al, 2008;Futaki et al, 2005;Yamada et al, 2012b). A number of nanoparticles were observed to accumulate around the nucleus where most of the mitochondria are located (Fig.…”

Section: Cell Viability and Intracellular Observation Of Df-mito-portermentioning

confidence: 99%

Mitochondrial targeting functional peptides as potential devices for the mitochondrial delivery of a DF-MITO-Porter

2013

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To achieve mitochondrial therapy, we previously reported on the use of an octaarginine (R8) modified Dual Function (DF)-MITO-Porter for delivering molecules to mitochondria in living cells. In this study, using isolated mitochondria, homogenates and living cells, we evaluated the utility of mitochondrial targeting functional peptides as a ligand for delivering carriers. The S2 peptide modified carrier showed a high mitochondrial targeting activity in homogenates and living cells. In addition, the S2 peptide had a lower cell toxicity compared to R8 modified liposomes. The S2 peptide represents a potentially useful moiety for constructing an efficient and safe mitochondrial delivery system.

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Unique features of a pH-sensitive fusogenic peptide that improves the transfection efficiency of cationic liposomes

Abstract: The unique features of GALA to mediate improved transfection efficiencies were identified.

Cited by 67 publications

References 15 publications

Inhibition of brain tumor growth by intravenous poly(β- l -malic acid) nanobioconjugate with pH-dependent drug release

Inhibition of brain tumor growth by intravenous poly(β- l -malic acid) nanobioconjugate with pH-dependent drug release

Hyaluronic acid controls the uptake pathway and intracellular trafficking of an octaarginine-modified gene vector in CD44 positive- and CD44 negative-cells

Mitochondrial targeting functional peptides as potential devices for the mitochondrial delivery of a DF-MITO-Porter

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