Novel cationic polyene glycol phospholipids as DNA transfer reagents - Lack of a structure-activity relationship due to uncontrolled self-assembling processes

Christer L. Opstad, Muhammad Zeeshan, Asma Zaidi, Hans Richard Sliwka, Vassilia Partali, David G. Nicholson, Chinmay Surve, Mitchell A. Izower, Natalia Bilchuk, Howard H. Lou, Philip L. Leopold, Helge Larsen, Aleksandra Liberska, Nada Abdul Khalique, Liji Raju, Marcella Flinterman, Emile Jubeli, Michael D. Pungente

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Cationic glycol phospholipids were synthesized introducing chromophoric, rigid polyenoic C20:5 and C30:9 chains next to saturated flexible alkyl chains of variable lengths C6-20:0. Surface properties and liposome formation of the amphiphilic compounds were determined, the properties of liposome/DNA complexes (lipoplexes) were established using three formulations (no co-lipid, DOPE as a co-lipid, or cholesterol as a co-lipid), and the microstructure of the best transfecting compounds inspected using small angle X-ray diffraction to explore details of the partially ordered structures of the systems that constitute the series. Transfection and cytotoxicity of the lipoplexes were evaluated by DNA delivery to Chinese hamster ovary (CHO-K1) cells using the cationic glycerol phospholipid 1,2-dioleoyl-sn-glycero-3- ethylphosphocholine (EPC) as a reference compound. The uncontrollable self-association of the molecules in water resulted in aggregates and liposomes of quite different sizes without a structure-property relationship. Likewise, adding DNA to the liposomes gave rise to unpredictable sized lipoplexes, which, again, transfected without a structure-activity relationship. Nevertheless, one compound among the novel lipids (C30:9 chain paired with a C 20:0 chain) exhibited comparable transfection efficiency and toxicity to the control cationic lipid EPC. Thus, the presence of a rigid polyene chain in this best performing achiral glycol lipid did not have an influence on transfection compared with the chiral glycerolipid reference ethyl phosphocholine EPC with two flexible saturated C14 chains.

Original languageEnglish
Pages (from-to)117-136
Number of pages20
JournalChemistry and Physics of Lipids
Volume183
DOIs
Publication statusPublished - 1 Jan 2014
Externally publishedYes

Fingerprint

Polyenes
Glycols
Structure-Activity Relationship
Liposomes
Phospholipids
Lipids
DNA
Transfection
Phosphorylcholine
Surface Properties
CHO Cells
Cytotoxicity
Cricetulus
X-Ray Diffraction
Glycerol
Surface properties
Toxicity
Ovary
Cholesterol
X ray diffraction

Keywords

  • Aggregation
  • Amphiphiles
  • Carotenoids
  • Cations
  • DNA
  • Lipids

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Cell Biology

Cite this

Novel cationic polyene glycol phospholipids as DNA transfer reagents - Lack of a structure-activity relationship due to uncontrolled self-assembling processes. / Opstad, Christer L.; Zeeshan, Muhammad; Zaidi, Asma; Sliwka, Hans Richard; Partali, Vassilia; Nicholson, David G.; Surve, Chinmay; Izower, Mitchell A.; Bilchuk, Natalia; Lou, Howard H.; Leopold, Philip L.; Larsen, Helge; Liberska, Aleksandra; Khalique, Nada Abdul; Raju, Liji; Flinterman, Marcella; Jubeli, Emile; Pungente, Michael D.

In: Chemistry and Physics of Lipids, Vol. 183, 01.01.2014, p. 117-136.

Research output: Contribution to journalArticle

Opstad, CL, Zeeshan, M, Zaidi, A, Sliwka, HR, Partali, V, Nicholson, DG, Surve, C, Izower, MA, Bilchuk, N, Lou, HH, Leopold, PL, Larsen, H, Liberska, A, Khalique, NA, Raju, L, Flinterman, M, Jubeli, E & Pungente, MD 2014, 'Novel cationic polyene glycol phospholipids as DNA transfer reagents - Lack of a structure-activity relationship due to uncontrolled self-assembling processes', Chemistry and Physics of Lipids, vol. 183, pp. 117-136. https://doi.org/10.1016/j.chemphyslip.2014.04.006
Opstad, Christer L. ; Zeeshan, Muhammad ; Zaidi, Asma ; Sliwka, Hans Richard ; Partali, Vassilia ; Nicholson, David G. ; Surve, Chinmay ; Izower, Mitchell A. ; Bilchuk, Natalia ; Lou, Howard H. ; Leopold, Philip L. ; Larsen, Helge ; Liberska, Aleksandra ; Khalique, Nada Abdul ; Raju, Liji ; Flinterman, Marcella ; Jubeli, Emile ; Pungente, Michael D. / Novel cationic polyene glycol phospholipids as DNA transfer reagents - Lack of a structure-activity relationship due to uncontrolled self-assembling processes. In: Chemistry and Physics of Lipids. 2014 ; Vol. 183. pp. 117-136.
@article{df33363bfc2e4481804b29a4e0aa79d1,
title = "Novel cationic polyene glycol phospholipids as DNA transfer reagents - Lack of a structure-activity relationship due to uncontrolled self-assembling processes",
abstract = "Cationic glycol phospholipids were synthesized introducing chromophoric, rigid polyenoic C20:5 and C30:9 chains next to saturated flexible alkyl chains of variable lengths C6-20:0. Surface properties and liposome formation of the amphiphilic compounds were determined, the properties of liposome/DNA complexes (lipoplexes) were established using three formulations (no co-lipid, DOPE as a co-lipid, or cholesterol as a co-lipid), and the microstructure of the best transfecting compounds inspected using small angle X-ray diffraction to explore details of the partially ordered structures of the systems that constitute the series. Transfection and cytotoxicity of the lipoplexes were evaluated by DNA delivery to Chinese hamster ovary (CHO-K1) cells using the cationic glycerol phospholipid 1,2-dioleoyl-sn-glycero-3- ethylphosphocholine (EPC) as a reference compound. The uncontrollable self-association of the molecules in water resulted in aggregates and liposomes of quite different sizes without a structure-property relationship. Likewise, adding DNA to the liposomes gave rise to unpredictable sized lipoplexes, which, again, transfected without a structure-activity relationship. Nevertheless, one compound among the novel lipids (C30:9 chain paired with a C 20:0 chain) exhibited comparable transfection efficiency and toxicity to the control cationic lipid EPC. Thus, the presence of a rigid polyene chain in this best performing achiral glycol lipid did not have an influence on transfection compared with the chiral glycerolipid reference ethyl phosphocholine EPC with two flexible saturated C14 chains.",
keywords = "Aggregation, Amphiphiles, Carotenoids, Cations, DNA, Lipids",
author = "Opstad, {Christer L.} and Muhammad Zeeshan and Asma Zaidi and Sliwka, {Hans Richard} and Vassilia Partali and Nicholson, {David G.} and Chinmay Surve and Izower, {Mitchell A.} and Natalia Bilchuk and Lou, {Howard H.} and Leopold, {Philip L.} and Helge Larsen and Aleksandra Liberska and Khalique, {Nada Abdul} and Liji Raju and Marcella Flinterman and Emile Jubeli and Pungente, {Michael D.}",
year = "2014",
month = "1",
day = "1",
doi = "10.1016/j.chemphyslip.2014.04.006",
language = "English",
volume = "183",
pages = "117--136",
journal = "Chemistry and Physics of Lipids",
issn = "0009-3084",
publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - Novel cationic polyene glycol phospholipids as DNA transfer reagents - Lack of a structure-activity relationship due to uncontrolled self-assembling processes

AU - Opstad, Christer L.

AU - Zeeshan, Muhammad

AU - Zaidi, Asma

AU - Sliwka, Hans Richard

AU - Partali, Vassilia

AU - Nicholson, David G.

AU - Surve, Chinmay

AU - Izower, Mitchell A.

AU - Bilchuk, Natalia

AU - Lou, Howard H.

AU - Leopold, Philip L.

AU - Larsen, Helge

AU - Liberska, Aleksandra

AU - Khalique, Nada Abdul

AU - Raju, Liji

AU - Flinterman, Marcella

AU - Jubeli, Emile

AU - Pungente, Michael D.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Cationic glycol phospholipids were synthesized introducing chromophoric, rigid polyenoic C20:5 and C30:9 chains next to saturated flexible alkyl chains of variable lengths C6-20:0. Surface properties and liposome formation of the amphiphilic compounds were determined, the properties of liposome/DNA complexes (lipoplexes) were established using three formulations (no co-lipid, DOPE as a co-lipid, or cholesterol as a co-lipid), and the microstructure of the best transfecting compounds inspected using small angle X-ray diffraction to explore details of the partially ordered structures of the systems that constitute the series. Transfection and cytotoxicity of the lipoplexes were evaluated by DNA delivery to Chinese hamster ovary (CHO-K1) cells using the cationic glycerol phospholipid 1,2-dioleoyl-sn-glycero-3- ethylphosphocholine (EPC) as a reference compound. The uncontrollable self-association of the molecules in water resulted in aggregates and liposomes of quite different sizes without a structure-property relationship. Likewise, adding DNA to the liposomes gave rise to unpredictable sized lipoplexes, which, again, transfected without a structure-activity relationship. Nevertheless, one compound among the novel lipids (C30:9 chain paired with a C 20:0 chain) exhibited comparable transfection efficiency and toxicity to the control cationic lipid EPC. Thus, the presence of a rigid polyene chain in this best performing achiral glycol lipid did not have an influence on transfection compared with the chiral glycerolipid reference ethyl phosphocholine EPC with two flexible saturated C14 chains.

AB - Cationic glycol phospholipids were synthesized introducing chromophoric, rigid polyenoic C20:5 and C30:9 chains next to saturated flexible alkyl chains of variable lengths C6-20:0. Surface properties and liposome formation of the amphiphilic compounds were determined, the properties of liposome/DNA complexes (lipoplexes) were established using three formulations (no co-lipid, DOPE as a co-lipid, or cholesterol as a co-lipid), and the microstructure of the best transfecting compounds inspected using small angle X-ray diffraction to explore details of the partially ordered structures of the systems that constitute the series. Transfection and cytotoxicity of the lipoplexes were evaluated by DNA delivery to Chinese hamster ovary (CHO-K1) cells using the cationic glycerol phospholipid 1,2-dioleoyl-sn-glycero-3- ethylphosphocholine (EPC) as a reference compound. The uncontrollable self-association of the molecules in water resulted in aggregates and liposomes of quite different sizes without a structure-property relationship. Likewise, adding DNA to the liposomes gave rise to unpredictable sized lipoplexes, which, again, transfected without a structure-activity relationship. Nevertheless, one compound among the novel lipids (C30:9 chain paired with a C 20:0 chain) exhibited comparable transfection efficiency and toxicity to the control cationic lipid EPC. Thus, the presence of a rigid polyene chain in this best performing achiral glycol lipid did not have an influence on transfection compared with the chiral glycerolipid reference ethyl phosphocholine EPC with two flexible saturated C14 chains.

KW - Aggregation

KW - Amphiphiles

KW - Carotenoids

KW - Cations

KW - DNA

KW - Lipids

UR - http://www.scopus.com/inward/record.url?scp=84903191861&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84903191861&partnerID=8YFLogxK

U2 - 10.1016/j.chemphyslip.2014.04.006

DO - 10.1016/j.chemphyslip.2014.04.006

M3 - Article

C2 - 24814958

AN - SCOPUS:84903191861

VL - 183

SP - 117

EP - 136

JO - Chemistry and Physics of Lipids

JF - Chemistry and Physics of Lipids

SN - 0009-3084

ER -