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Development of a novel systemic gene delivery system for cancer therapy with a tumor-specific cleavable PEG-lipid

For successful cancer gene therapy via intravenous (i.v.) administration, it is essential to optimize the stability of carriers in the systemic circulation and the cellular association after the accumulation of the carrier in tumor tissue. However, a dilemma exists regarding the use of poly(ethylene... Full description

Journal Title: Gene Therapy Jan 2007, Vol.14(1), pp.68-77
Main Author: Hatakeyama, H
Other Authors: Akita, H , Kogure, K , Oishi, M , Nagasaki, Y , Kihira, Y , Ueno, M , Kobayashi, H , Kikuchi, H , Harashima, H
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 09697128 ; DOI: 10.1038/sj.gt.3302843
Link: http://search.proquest.com/docview/218715376/?pq-origsite=primo
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title: Development of a novel systemic gene delivery system for cancer therapy with a tumor-specific cleavable PEG-lipid
format: Article
creator:
  • Hatakeyama, H
  • Akita, H
  • Kogure, K
  • Oishi, M
  • Nagasaki, Y
  • Kihira, Y
  • Ueno, M
  • Kobayashi, H
  • Kikuchi, H
  • Harashima, H
subjects:
  • Animals–Methods
  • Cell Line, Tumor–Administration & Dosage
  • Drug Carriers–Administration & Dosage
  • Freeze Fracturing–Genetics
  • Gene Expression–Analysis
  • Gene Targeting–Metabolism
  • Genetic Engineering–Enzymology
  • Genetic Therapy–Metabolism
  • Genetic Vectors–Therapy
  • Half-Life–Genetics
  • Humans–Metabolism
  • Injections, Intravenous–Administration & Dosage
  • Liposomes–Metabolism
  • Luciferases–Methods
  • Magnetic Resonance Spectroscopy–Methods
  • Male–Methods
  • Matrix Metalloproteinase 2–Methods
  • Matrix Metalloproteinase 2–Methods
  • Mice–Methods
  • Mice, Nude–Methods
  • Microscopy, Electron–Methods
  • Neoplasm Transplantation–Methods
  • Neoplasms–Methods
  • Neoplasms–Methods
  • Neoplasms–Methods
  • Phosphatidylethanolamines–Methods
  • Phosphatidylethanolamines–Methods
  • Polyethylene Glycols–Methods
  • Polyethylene Glycols–Methods
  • Transfection–Methods
  • Gene Therapy
  • Cancer
  • Tumors
  • Lipids
  • Medical Treatment
  • Tissue
  • Peptides
  • Gene Expression
  • 1,2-Dioleoyl-Glycero-3-Phosphatidyl Ethanolamine
  • Drug Carriers
  • Liposomes
  • Phosphatidylethanolamines
  • Polyethylene Glycols
  • Luciferases
  • Matrix Metalloproteinase 2
ispartof: Gene Therapy, Jan 2007, Vol.14(1), pp.68-77
description: For successful cancer gene therapy via intravenous (i.v.) administration, it is essential to optimize the stability of carriers in the systemic circulation and the cellular association after the accumulation of the carrier in tumor tissue. However, a dilemma exists regarding the use of poly(ethylene glycol) (PEG), which is useful for conferring stability in the systemic circulation, but is undesirable for the cellular uptake and the following processes. We report the development of a PEG-peptide-lipid ternary conjugate (PEG-Peptide-DOPE conjugate (PPD)). In this strategy, the PEG is removed from the carriers via cleavage by a matrix metalloproteinase (MMP), which is specifically expressed in tumor tissues. An in vitro study revealed that the PPD-modified gene carrier (Multifunctional Envelope-type Nano Device: MEND) exhibited pDNA expression activity that was dependent on the MMP expression level in the host cells. In vivo studies further revealed that the PPD was potent in stabilizing MEND in the systemic circulation and facilitating tumor accumulation. Moreover, the i.v. administration of PPD or PEG/PPD dually-modified MEND resulted in the stimulation of pDNA expression in tumor tissue, as compared with a conventional PEG-modified MEND. Thus, MEND modified with PPD is a promising device, which has the potential to make in vivo cancer gene therapy achievable.
language: eng
source:
identifier: ISSN: 09697128 ; DOI: 10.1038/sj.gt.3302843
fulltext: fulltext
issn:
  • 09697128
  • 0969-7128
url: Link


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titleDevelopment of a novel systemic gene delivery system for cancer therapy with a tumor-specific cleavable PEG-lipid
creatorHatakeyama, H ; Akita, H ; Kogure, K ; Oishi, M ; Nagasaki, Y ; Kihira, Y ; Ueno, M ; Kobayashi, H ; Kikuchi, H ; Harashima, H
ispartofGene Therapy, Jan 2007, Vol.14(1), pp.68-77
identifierISSN: 09697128 ; DOI: 10.1038/sj.gt.3302843
subjectAnimals–Methods ; Cell Line, Tumor–Administration & Dosage ; Drug Carriers–Administration & Dosage ; Freeze Fracturing–Genetics ; Gene Expression–Analysis ; Gene Targeting–Metabolism ; Genetic Engineering–Enzymology ; Genetic Therapy–Metabolism ; Genetic Vectors–Therapy ; Half-Life–Genetics ; Humans–Metabolism ; Injections, Intravenous–Administration & Dosage ; Liposomes–Metabolism ; Luciferases–Methods ; Magnetic Resonance Spectroscopy–Methods ; Male–Methods ; Matrix Metalloproteinase 2–Methods ; Matrix Metalloproteinase 2–Methods ; Mice–Methods ; Mice, Nude–Methods ; Microscopy, Electron–Methods ; Neoplasm Transplantation–Methods ; Neoplasms–Methods ; Neoplasms–Methods ; Neoplasms–Methods ; Phosphatidylethanolamines–Methods ; Phosphatidylethanolamines–Methods ; Polyethylene Glycols–Methods ; Polyethylene Glycols–Methods ; Transfection–Methods ; Gene Therapy ; Cancer ; Tumors ; Lipids ; Medical Treatment ; Tissue ; Peptides ; Gene Expression ; 1,2-Dioleoyl-Glycero-3-Phosphatidyl Ethanolamine ; Drug Carriers ; Liposomes ; Phosphatidylethanolamines ; Polyethylene Glycols ; Luciferases ; Matrix Metalloproteinase 2
descriptionFor successful cancer gene therapy via intravenous (i.v.) administration, it is essential to optimize the stability of carriers in the systemic circulation and the cellular association after the accumulation of the carrier in tumor tissue. However, a dilemma exists regarding the use of poly(ethylene glycol) (PEG), which is useful for conferring stability in the systemic circulation, but is undesirable for the cellular uptake and the following processes. We report the development of a PEG-peptide-lipid ternary conjugate (PEG-Peptide-DOPE conjugate (PPD)). In this strategy, the PEG is removed from the carriers via cleavage by a matrix metalloproteinase (MMP), which is specifically expressed in tumor tissues. An in vitro study revealed that the PPD-modified gene carrier (Multifunctional Envelope-type Nano Device: MEND) exhibited pDNA expression activity that was dependent on the MMP expression level in the host cells. In vivo studies further revealed that the PPD was potent in stabilizing MEND in the systemic circulation and facilitating tumor accumulation. Moreover, the i.v. administration of PPD or PEG/PPD dually-modified MEND resulted in the stimulation of pDNA expression in tumor tissue, as compared with a conventional PEG-modified MEND. Thus, MEND modified with PPD is a promising device, which has the potential to make in vivo cancer gene therapy achievable.
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titleDevelopment of a novel systemic gene delivery system for cancer therapy with a tumor-specific cleavable PEG-lipid
descriptionFor successful cancer gene therapy via intravenous (i.v.) administration, it is essential to optimize the stability of carriers in the systemic circulation and the cellular association after the accumulation of the carrier in tumor tissue. However, a dilemma exists regarding the use of poly(ethylene glycol) (PEG), which is useful for conferring stability in the systemic circulation, but is undesirable for the cellular uptake and the following processes. We report the development of a PEG-peptide-lipid ternary conjugate (PEG-Peptide-DOPE conjugate (PPD)). In this strategy, the PEG is removed from the carriers via cleavage by a matrix metalloproteinase (MMP), which is specifically expressed in tumor tissues. An in vitro study revealed that the PPD-modified gene carrier (Multifunctional Envelope-type Nano Device: MEND) exhibited pDNA expression activity that was dependent on the MMP expression level in the host cells. In vivo studies further revealed that the PPD was potent in stabilizing MEND in the systemic circulation and facilitating tumor accumulation. Moreover, the i.v. administration of PPD or PEG/PPD dually-modified MEND resulted in the stimulation of pDNA expression in tumor tissue, as compared with a conventional PEG-modified MEND. Thus, MEND modified with PPD is a promising device, which has the potential to make in vivo cancer gene therapy achievable.
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9Half-Life–Genetics
10Humans–Metabolism
11Injections, Intravenous–Administration & Dosage
12Liposomes–Metabolism
13Luciferases–Methods
14Magnetic Resonance Spectroscopy–Methods
15Male–Methods
16Matrix Metalloproteinase 2–Methods
17Mice–Methods
18Mice, Nude–Methods
19Microscopy, Electron–Methods
20Neoplasm Transplantation–Methods
21Neoplasms–Methods
22Phosphatidylethanolamines–Methods
23Polyethylene Glycols–Methods
24Transfection–Methods
25Gene Therapy
26Cancer
27Tumors
28Lipids
29Medical Treatment
30Tissue
31Peptides
32Gene Expression
331,2-Dioleoyl-Glycero-3-Phosphatidyl Ethanolamine
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35Liposomes
36Phosphatidylethanolamines
37Polyethylene Glycols
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titleDevelopment of a novel systemic gene delivery system for cancer therapy with a tumor-specific cleavable PEG-lipid
authorHatakeyama, H ; Akita, H ; Kogure, K ; Oishi, M ; Nagasaki, Y ; Kihira, Y ; Ueno, M ; Kobayashi, H ; Kikuchi, H ; Harashima, H
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1Cell Line, Tumor–Administration & Dosage
2Drug Carriers–Administration & Dosage
3Freeze Fracturing–Genetics
4Gene Expression–Analysis
5Gene Targeting–Metabolism
6Genetic Engineering–Enzymology
7Genetic Therapy–Metabolism
8Genetic Vectors–Therapy
9Half-Life–Genetics
10Humans–Metabolism
11Injections, Intravenous–Administration & Dosage
12Liposomes–Metabolism
13Luciferases–Methods
14Magnetic Resonance Spectroscopy–Methods
15Male–Methods
16Matrix Metalloproteinase 2–Methods
17Mice–Methods
18Mice, Nude–Methods
19Microscopy, Electron–Methods
20Neoplasm Transplantation–Methods
21Neoplasms–Methods
22Phosphatidylethanolamines–Methods
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30Tissue
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331,2-Dioleoyl-Glycero-3-Phosphatidyl Ethanolamine
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abstractFor successful cancer gene therapy via intravenous (i.v.) administration, it is essential to optimize the stability of carriers in the systemic circulation and the cellular association after the accumulation of the carrier in tumor tissue. However, a dilemma exists regarding the use of poly(ethylene glycol) (PEG), which is useful for conferring stability in the systemic circulation, but is undesirable for the cellular uptake and the following processes. We report the development of a PEG-peptide-lipid ternary conjugate (PEG-Peptide-DOPE conjugate (PPD)). In this strategy, the PEG is removed from the carriers via cleavage by a matrix metalloproteinase (MMP), which is specifically expressed in tumor tissues. An in vitro study revealed that the PPD-modified gene carrier (Multifunctional Envelope-type Nano Device: MEND) exhibited pDNA expression activity that was dependent on the MMP expression level in the host cells. In vivo studies further revealed that the PPD was potent in stabilizing MEND in the systemic circulation and facilitating tumor accumulation. Moreover, the i.v. administration of PPD or PEG/PPD dually-modified MEND resulted in the stimulation of pDNA expression in tumor tissue, as compared with a conventional PEG-modified MEND. Thus, MEND modified with PPD is a promising device, which has the potential to make in vivo cancer gene therapy achievable.
copHoundmills
pubNature Publishing Group
doi10.1038/sj.gt.3302843
urlhttp://search.proquest.com/docview/218715376/
eissn14765462
date2007-01-01