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Tumor-specific gene transfer with receptor-mediated nanocomplexes modified by polyethylene glycol shielding and endosomally cleavable lipid and peptide linkers.

Synthetic nanoparticle formulations have the potential for tumor-targeted gene delivery. Receptor-targeted nanocomplex (RTN) formulations comprise mixtures of cationic liposomes and targeting peptides that self-assemble on mixing with nucleic acids. RTN formulations were prepared containing differen... Full description

Journal Title: FASEB journal : official publication of the Federation of American Societies for Experimental Biology July 2010, Vol.24(7), pp.2301-2313
Main Author: Grosse, Stephanie M
Other Authors: Tagalakis, Aristides D , Mustapa, M Firouz Mohd , Elbs, Martin , Meng, Qing-Hai , Mohammadi, Atefeh , Tabor, Alethea B , Hailes, Helen C , Hart, Stephen L
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1530-6860 ; DOI: 10.1096/fj.09-144220
Link: http://search.proquest.com/docview/733566508/?pq-origsite=primo
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recordid: proquest733566508
title: Tumor-specific gene transfer with receptor-mediated nanocomplexes modified by polyethylene glycol shielding and endosomally cleavable lipid and peptide linkers.
format: Article
creator:
  • Grosse, Stephanie M
  • Tagalakis, Aristides D
  • Mustapa, M Firouz Mohd
  • Elbs, Martin
  • Meng, Qing-Hai
  • Mohammadi, Atefeh
  • Tabor, Alethea B
  • Hailes, Helen C
  • Hart, Stephen L
subjects:
  • Animals–Administration & Dosage
  • Antineoplastic Agents–Methods
  • Cell Line, Tumor–Metabolism
  • Cells, Cultured–Chemistry
  • Drug Delivery Systems–Therapeutic Use
  • Endosomes–Pathology
  • Gene Transfer Techniques–Pathology
  • Hydrolysis–Pathology
  • Lipids–Pathology
  • Mice–Pathology
  • Nanoparticles–Pathology
  • Neuroblastoma–Pathology
  • Peptides–Pathology
  • Polyethylene Glycols–Pathology
  • Prodrugs–Pathology
  • Swine–Pathology
  • Antineoplastic Agents
  • Lipids
  • Peptides
  • Prodrugs
  • Polyethylene Glycols
ispartof: FASEB journal : official publication of the Federation of American Societies for Experimental Biology, July 2010, Vol.24(7), pp.2301-2313
description: Synthetic nanoparticle formulations have the potential for tumor-targeted gene delivery. Receptor-targeted nanocomplex (RTN) formulations comprise mixtures of cationic liposomes and targeting peptides that self-assemble on mixing with nucleic acids. RTN formulations were prepared containing different polyethylene glycol (PEG)ylated lipids with esterase-cleavable linkers (e.g., ME42) to promote intracellular PEG detachment and nanoparticle disassembly. In addition, integrin-targeting peptides (peptide ME27) were tested with endosomal furin- and cathepsin B-cleavable peptide linkers located between the integrin-binding ligand and the K(16) nucleic acid-binding domain to promote intracellular disengagement from the receptor. ME42/ME27 RTNs formed stable particles of
language: eng
source:
identifier: E-ISSN: 1530-6860 ; DOI: 10.1096/fj.09-144220
fulltext: fulltext
issn:
  • 15306860
  • 1530-6860
url: Link


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titleTumor-specific gene transfer with receptor-mediated nanocomplexes modified by polyethylene glycol shielding and endosomally cleavable lipid and peptide linkers.
creatorGrosse, Stephanie M ; Tagalakis, Aristides D ; Mustapa, M Firouz Mohd ; Elbs, Martin ; Meng, Qing-Hai ; Mohammadi, Atefeh ; Tabor, Alethea B ; Hailes, Helen C ; Hart, Stephen L
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ispartofFASEB journal : official publication of the Federation of American Societies for Experimental Biology, July 2010, Vol.24(7), pp.2301-2313
identifierE-ISSN: 1530-6860 ; DOI: 10.1096/fj.09-144220
subjectAnimals–Administration & Dosage ; Antineoplastic Agents–Methods ; Cell Line, Tumor–Metabolism ; Cells, Cultured–Chemistry ; Drug Delivery Systems–Therapeutic Use ; Endosomes–Pathology ; Gene Transfer Techniques–Pathology ; Hydrolysis–Pathology ; Lipids–Pathology ; Mice–Pathology ; Nanoparticles–Pathology ; Neuroblastoma–Pathology ; Peptides–Pathology ; Polyethylene Glycols–Pathology ; Prodrugs–Pathology ; Swine–Pathology ; Antineoplastic Agents ; Lipids ; Peptides ; Prodrugs ; Polyethylene Glycols
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descriptionSynthetic nanoparticle formulations have the potential for tumor-targeted gene delivery. Receptor-targeted nanocomplex (RTN) formulations comprise mixtures of cationic liposomes and targeting peptides that self-assemble on mixing with nucleic acids. RTN formulations were prepared containing different polyethylene glycol (PEG)ylated lipids with esterase-cleavable linkers (e.g., ME42) to promote intracellular PEG detachment and nanoparticle disassembly. In addition, integrin-targeting peptides (peptide ME27) were tested with endosomal furin- and cathepsin B-cleavable peptide linkers located between the integrin-binding ligand and the K(16) nucleic acid-binding domain to promote intracellular disengagement from the receptor. ME42/ME27 RTNs formed stable particles of <200 nm in isotonic salt buffers, compared with 4-microm particles formed by un-PEGylated RTNs. Transfection efficiency by PEG-modified, cleavable RTNs improved approximately 2-fold in 4 different cell lines, with 80% efficiency in murine neuroblastoma cells. In an in vivo model of neuroblastoma, ME42/ME27 RTNs delivering luciferase genes were tumor specific, with little expression in other organs tested. PEGylation of the RTNs enhanced luciferase transfection 5-fold over non-PEG formulations, whereas the cleavability of the peptide ME27 enhanced transfection 4-fold over that of RTNs with noncleavable peptides. Cleavability of the lipid for in vivo transfections had no effect. PEGylated, cleavable RTN formulations offer prospects for tumor-specific therapeutic gene transfer.
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titleTumor-specific gene transfer with receptor-mediated nanocomplexes modified by polyethylene glycol shielding and endosomally cleavable lipid and peptide linkers.
authorGrosse, Stephanie M ; Tagalakis, Aristides D ; Mustapa, M Firouz Mohd ; Elbs, Martin ; Meng, Qing-Hai ; Mohammadi, Atefeh ; Tabor, Alethea B ; Hailes, Helen C ; Hart, Stephen L
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