Examination of structure-activity relationship of viologen-based dendrimers as cxcr4 antagonists and gene carriers

Jing Li, Ana Maria Lepadatu, Yu Zhu, Marius Ciobanu, Yan Wang, Simona C. Asaftei, David Oupicky

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Chemokine receptors and their ligands play a central role in cancer metastasis, inflammatory disorders, and viral infections. Viologen dendrimers (VGD) emerged recently as a promising class of synthetic polycationic ligands for chemokine receptor CXCR4. The objective of this study was to evaluate the potential of VGD as novel dual-function polycations capable of simultaneous CXCR4 antagonism and gene delivery. As part of our systematic studies, we have synthesized a library of VGD with differences in molecular architecture, number of positive charges, and type of capping group. The ability of VGD to condense DNA was evaluated, and physicochemical and biological properties of the resulting polyplexes were studied. We have evaluated the effect of VGD surface charge, size, capping group, and molecular architecture on physicochemical properties of polyplexes, transfection efficiency, CXCR4 antagonism, and cytotoxicity in human epithelial osteosarcoma (U2OS) and in human liver hepatocellular carcinoma (HepG2) cells. We found that properties and behavior of the polyplexes are most dependent on the number of positive charges and molecular weight of VGD and to a lesser extent on the type of a capping group. Using TNFα plasmid, we have demonstrated that VGD prevents CXCR4-mediated cancer cell invasion and facilitates TNFα-mediated cancer cell killing. Such dual-function carriers have potential to enhance the overall therapeutic outcomes of cancer gene therapy.

Original languageEnglish (US)
Pages (from-to)907-917
Number of pages11
JournalBioconjugate Chemistry
Volume25
Issue number5
DOIs
StatePublished - May 21 2014

Fingerprint

Viologens
Dendrimers
Structure-Activity Relationship
Genes
Chemokine Receptors
Ligands
Cells
Gene therapy
Neoplasms
Aptitude
Neoplasm Genes
Hep G2 Cells
Virus Diseases
Osteosarcoma
Cytotoxicity
Surface charge
Genetic Therapy
Liver
Libraries
Transfection

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

Cite this

Examination of structure-activity relationship of viologen-based dendrimers as cxcr4 antagonists and gene carriers. / Li, Jing; Lepadatu, Ana Maria; Zhu, Yu; Ciobanu, Marius; Wang, Yan; Asaftei, Simona C.; Oupicky, David.

In: Bioconjugate Chemistry, Vol. 25, No. 5, 21.05.2014, p. 907-917.

Research output: Contribution to journalArticle

Li, Jing ; Lepadatu, Ana Maria ; Zhu, Yu ; Ciobanu, Marius ; Wang, Yan ; Asaftei, Simona C. ; Oupicky, David. / Examination of structure-activity relationship of viologen-based dendrimers as cxcr4 antagonists and gene carriers. In: Bioconjugate Chemistry. 2014 ; Vol. 25, No. 5. pp. 907-917.
@article{7fa72c68757f488e86a15951970066d8,
title = "Examination of structure-activity relationship of viologen-based dendrimers as cxcr4 antagonists and gene carriers",
abstract = "Chemokine receptors and their ligands play a central role in cancer metastasis, inflammatory disorders, and viral infections. Viologen dendrimers (VGD) emerged recently as a promising class of synthetic polycationic ligands for chemokine receptor CXCR4. The objective of this study was to evaluate the potential of VGD as novel dual-function polycations capable of simultaneous CXCR4 antagonism and gene delivery. As part of our systematic studies, we have synthesized a library of VGD with differences in molecular architecture, number of positive charges, and type of capping group. The ability of VGD to condense DNA was evaluated, and physicochemical and biological properties of the resulting polyplexes were studied. We have evaluated the effect of VGD surface charge, size, capping group, and molecular architecture on physicochemical properties of polyplexes, transfection efficiency, CXCR4 antagonism, and cytotoxicity in human epithelial osteosarcoma (U2OS) and in human liver hepatocellular carcinoma (HepG2) cells. We found that properties and behavior of the polyplexes are most dependent on the number of positive charges and molecular weight of VGD and to a lesser extent on the type of a capping group. Using TNFα plasmid, we have demonstrated that VGD prevents CXCR4-mediated cancer cell invasion and facilitates TNFα-mediated cancer cell killing. Such dual-function carriers have potential to enhance the overall therapeutic outcomes of cancer gene therapy.",
author = "Jing Li and Lepadatu, {Ana Maria} and Yu Zhu and Marius Ciobanu and Yan Wang and Asaftei, {Simona C.} and David Oupicky",
year = "2014",
month = "5",
day = "21",
doi = "10.1021/bc500191q",
language = "English (US)",
volume = "25",
pages = "907--917",
journal = "Bioconjugate Chemistry",
issn = "1043-1802",
publisher = "American Chemical Society",
number = "5",

}

TY - JOUR

T1 - Examination of structure-activity relationship of viologen-based dendrimers as cxcr4 antagonists and gene carriers

AU - Li, Jing

AU - Lepadatu, Ana Maria

AU - Zhu, Yu

AU - Ciobanu, Marius

AU - Wang, Yan

AU - Asaftei, Simona C.

AU - Oupicky, David

PY - 2014/5/21

Y1 - 2014/5/21

N2 - Chemokine receptors and their ligands play a central role in cancer metastasis, inflammatory disorders, and viral infections. Viologen dendrimers (VGD) emerged recently as a promising class of synthetic polycationic ligands for chemokine receptor CXCR4. The objective of this study was to evaluate the potential of VGD as novel dual-function polycations capable of simultaneous CXCR4 antagonism and gene delivery. As part of our systematic studies, we have synthesized a library of VGD with differences in molecular architecture, number of positive charges, and type of capping group. The ability of VGD to condense DNA was evaluated, and physicochemical and biological properties of the resulting polyplexes were studied. We have evaluated the effect of VGD surface charge, size, capping group, and molecular architecture on physicochemical properties of polyplexes, transfection efficiency, CXCR4 antagonism, and cytotoxicity in human epithelial osteosarcoma (U2OS) and in human liver hepatocellular carcinoma (HepG2) cells. We found that properties and behavior of the polyplexes are most dependent on the number of positive charges and molecular weight of VGD and to a lesser extent on the type of a capping group. Using TNFα plasmid, we have demonstrated that VGD prevents CXCR4-mediated cancer cell invasion and facilitates TNFα-mediated cancer cell killing. Such dual-function carriers have potential to enhance the overall therapeutic outcomes of cancer gene therapy.

AB - Chemokine receptors and their ligands play a central role in cancer metastasis, inflammatory disorders, and viral infections. Viologen dendrimers (VGD) emerged recently as a promising class of synthetic polycationic ligands for chemokine receptor CXCR4. The objective of this study was to evaluate the potential of VGD as novel dual-function polycations capable of simultaneous CXCR4 antagonism and gene delivery. As part of our systematic studies, we have synthesized a library of VGD with differences in molecular architecture, number of positive charges, and type of capping group. The ability of VGD to condense DNA was evaluated, and physicochemical and biological properties of the resulting polyplexes were studied. We have evaluated the effect of VGD surface charge, size, capping group, and molecular architecture on physicochemical properties of polyplexes, transfection efficiency, CXCR4 antagonism, and cytotoxicity in human epithelial osteosarcoma (U2OS) and in human liver hepatocellular carcinoma (HepG2) cells. We found that properties and behavior of the polyplexes are most dependent on the number of positive charges and molecular weight of VGD and to a lesser extent on the type of a capping group. Using TNFα plasmid, we have demonstrated that VGD prevents CXCR4-mediated cancer cell invasion and facilitates TNFα-mediated cancer cell killing. Such dual-function carriers have potential to enhance the overall therapeutic outcomes of cancer gene therapy.

UR - http://www.scopus.com/inward/record.url?scp=84901054431&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84901054431&partnerID=8YFLogxK

U2 - 10.1021/bc500191q

DO - 10.1021/bc500191q

M3 - Article

VL - 25

SP - 907

EP - 917

JO - Bioconjugate Chemistry

JF - Bioconjugate Chemistry

SN - 1043-1802

IS - 5

ER -