Bisethylnorspermine lipopolyamine as potential delivery vector for combination drug/gene anticancer therapies

Yanmei Dong, Jing Li, Chao Wu, David Oupicky

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Purpose: To design novel synthetic gene delivery system in which the carrier molecule functions dually as a carrier and a cytotoxic agent targeting dysregulated polyamine metabolism in cancer. Methods: Bisethylnorspermine (BENSpm) lipopolyamine was synthesized and its toxicity evaluated by MTS assay in MCF-7 and MCF-10A cells. Transfection activity was determined using luciferase plasmid DNA. Results: Asymmetrical lipid analogue of polyamine anticancer drug BENSpm was synthesized using nucleophilic ring opening of azetidinium ion. The synthesized LipoBENSpm showed cytotoxicity comparable to that of parent BENSpm in human breast cancer cell line MCF-7 but mediated 3-4 orders magnitude higher transfection activity. Importantly, cytostatic activity of BENSpm, typically in a low μM range, falls within a relevant and typical concentration range required for efficient gene delivery. Conclusions: These findings make gene delivery vectors based on BENSpm promising candidates for combination drug/gene approaches to the treatment of cancer.

Original languageEnglish (US)
Pages (from-to)1927-1938
Number of pages12
JournalPharmaceutical Research
Volume27
Issue number9
DOIs
StatePublished - Sep 1 2010

Fingerprint

Antineoplastic Combined Chemotherapy Protocols
Gene therapy
Drug Combinations
Genetic Therapy
Genes
Polyamines
Transfection
Synthetic Genes
Gene Transfer Techniques
MCF-7 Cells
Cytotoxins
Cytostatic Agents
Luciferases
Neoplasms
Plasmids
Cytotoxicity
Metabolism
Ions
Breast Neoplasms
Toxicity

Keywords

  • drug combination
  • drug delivery
  • gene delivery
  • lipid
  • transfection

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Organic Chemistry
  • Molecular Medicine
  • Pharmacology (medical)
  • Biotechnology
  • Pharmacology

Cite this

Bisethylnorspermine lipopolyamine as potential delivery vector for combination drug/gene anticancer therapies. / Dong, Yanmei; Li, Jing; Wu, Chao; Oupicky, David.

In: Pharmaceutical Research, Vol. 27, No. 9, 01.09.2010, p. 1927-1938.

Research output: Contribution to journalArticle

@article{b7e790dcf40f47628ed7bb32b5fc7b7f,
title = "Bisethylnorspermine lipopolyamine as potential delivery vector for combination drug/gene anticancer therapies",
abstract = "Purpose: To design novel synthetic gene delivery system in which the carrier molecule functions dually as a carrier and a cytotoxic agent targeting dysregulated polyamine metabolism in cancer. Methods: Bisethylnorspermine (BENSpm) lipopolyamine was synthesized and its toxicity evaluated by MTS assay in MCF-7 and MCF-10A cells. Transfection activity was determined using luciferase plasmid DNA. Results: Asymmetrical lipid analogue of polyamine anticancer drug BENSpm was synthesized using nucleophilic ring opening of azetidinium ion. The synthesized LipoBENSpm showed cytotoxicity comparable to that of parent BENSpm in human breast cancer cell line MCF-7 but mediated 3-4 orders magnitude higher transfection activity. Importantly, cytostatic activity of BENSpm, typically in a low μM range, falls within a relevant and typical concentration range required for efficient gene delivery. Conclusions: These findings make gene delivery vectors based on BENSpm promising candidates for combination drug/gene approaches to the treatment of cancer.",
keywords = "drug combination, drug delivery, gene delivery, lipid, transfection",
author = "Yanmei Dong and Jing Li and Chao Wu and David Oupicky",
year = "2010",
month = "9",
day = "1",
doi = "10.1007/s11095-010-0197-4",
language = "English (US)",
volume = "27",
pages = "1927--1938",
journal = "Pharmaceutical Research",
issn = "0724-8741",
publisher = "Springer New York",
number = "9",

}

TY - JOUR

T1 - Bisethylnorspermine lipopolyamine as potential delivery vector for combination drug/gene anticancer therapies

AU - Dong, Yanmei

AU - Li, Jing

AU - Wu, Chao

AU - Oupicky, David

PY - 2010/9/1

Y1 - 2010/9/1

N2 - Purpose: To design novel synthetic gene delivery system in which the carrier molecule functions dually as a carrier and a cytotoxic agent targeting dysregulated polyamine metabolism in cancer. Methods: Bisethylnorspermine (BENSpm) lipopolyamine was synthesized and its toxicity evaluated by MTS assay in MCF-7 and MCF-10A cells. Transfection activity was determined using luciferase plasmid DNA. Results: Asymmetrical lipid analogue of polyamine anticancer drug BENSpm was synthesized using nucleophilic ring opening of azetidinium ion. The synthesized LipoBENSpm showed cytotoxicity comparable to that of parent BENSpm in human breast cancer cell line MCF-7 but mediated 3-4 orders magnitude higher transfection activity. Importantly, cytostatic activity of BENSpm, typically in a low μM range, falls within a relevant and typical concentration range required for efficient gene delivery. Conclusions: These findings make gene delivery vectors based on BENSpm promising candidates for combination drug/gene approaches to the treatment of cancer.

AB - Purpose: To design novel synthetic gene delivery system in which the carrier molecule functions dually as a carrier and a cytotoxic agent targeting dysregulated polyamine metabolism in cancer. Methods: Bisethylnorspermine (BENSpm) lipopolyamine was synthesized and its toxicity evaluated by MTS assay in MCF-7 and MCF-10A cells. Transfection activity was determined using luciferase plasmid DNA. Results: Asymmetrical lipid analogue of polyamine anticancer drug BENSpm was synthesized using nucleophilic ring opening of azetidinium ion. The synthesized LipoBENSpm showed cytotoxicity comparable to that of parent BENSpm in human breast cancer cell line MCF-7 but mediated 3-4 orders magnitude higher transfection activity. Importantly, cytostatic activity of BENSpm, typically in a low μM range, falls within a relevant and typical concentration range required for efficient gene delivery. Conclusions: These findings make gene delivery vectors based on BENSpm promising candidates for combination drug/gene approaches to the treatment of cancer.

KW - drug combination

KW - drug delivery

KW - gene delivery

KW - lipid

KW - transfection

UR - http://www.scopus.com/inward/record.url?scp=77955468323&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955468323&partnerID=8YFLogxK

U2 - 10.1007/s11095-010-0197-4

DO - 10.1007/s11095-010-0197-4

M3 - Article

VL - 27

SP - 1927

EP - 1938

JO - Pharmaceutical Research

JF - Pharmaceutical Research

SN - 0724-8741

IS - 9

ER -