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Prenyl Ammonium Salts--New Carriers for Gene Delivery: A B16-F10 Mouse Melanoma Model.

Grecka E, Statkiewicz M, Gorska A, Biernacka M, Grygorowicz MA, Masnyk M, Chmielewski M, Gawarecka K, Chojnacki T, Swiezewska E, Malecki M - PLoS ONE (2016)

Bottom Line: AP-15/DOPE complexes were also efficient to introduce pDNA to cells, without much effect on cell viability.Furthermore, complexes containing AP-15 and therapeutic plasmid, encoding the TIMP metallopeptidase inhibitor 2 (TIMP2), introduced the TIMP2 gene with high efficiency to B16-F10 melanoma cells but not to B16-F10 melanoma tumors in C57BL/6 mice, as confirmed by TIMP2 protein level determination.Obtained results indicate that APs have a potential as non-viral vectors for cell transfection.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.

ABSTRACT

Purpose: Prenyl ammonium iodides (Amino-Prenols, APs), semi-synthetic polyprenol derivatives were studied as prospective novel gene transfer agents.

Methods: AP-7, -8, -11 and -15 (aminoprenols composed of 7, 8, 11 or 15 isoprene units, respectively) were examined for their capacity to form complexes with pDNA, for cytotoxicity and ability to transfect genes to cells.

Results: All the carriers were able to complex DNA. The highest, comparable to commercial reagents, transfection efficiency was observed for AP-15. Simultaneously, AP-15 exhibited the lowest negative impact on cell viability and proliferation--considerably lower than that of commercial agents. AP-15/DOPE complexes were also efficient to introduce pDNA to cells, without much effect on cell viability. Transfection with AP-15/DOPE complexes influenced the expression of a very few among 44 tested genes involved in cellular lipid metabolism. Furthermore, complexes containing AP-15 and therapeutic plasmid, encoding the TIMP metallopeptidase inhibitor 2 (TIMP2), introduced the TIMP2 gene with high efficiency to B16-F10 melanoma cells but not to B16-F10 melanoma tumors in C57BL/6 mice, as confirmed by TIMP2 protein level determination.

Conclusion: Obtained results indicate that APs have a potential as non-viral vectors for cell transfection.

No MeSH data available.


Related in: MedlinePlus

Structure of Amino-Prenols, the AP molecule contains an polyisoprenoid chain composed of n isoprene residues.
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pone.0153633.g001: Structure of Amino-Prenols, the AP molecule contains an polyisoprenoid chain composed of n isoprene residues.

Mentions: Polyprenyltrimethylammonium iodides, further called Amino-Prenols (APs) are cationic, semi-synthetic derivatives of polyprenols (Fig 1) [10]. Polyprenols are common constituents of plant photosynthetic tissues (for review see [11]). Together with dolichols, typically found in mammalian tissues, they constitute a group of polyisoprenoid lipids. Besides their role as cofactors in protein glycosylation and prenylation [12] polyisoprenoid alcohols are postulated to act as membrane fluidizers, fusiogenic agents [13] and components of the intracellular protein-transporting machinery [14]. Taking into account their fusogenic activity a concept of the feasibility of cationic derivatives of polyprenol as components of lipofecting formula was proposed and appropriate studies have been initiated. As a result good efficacy of in vitro transfection with application of AP-7-based (aminoprenol composed of seven isoprene units) complexes has been demonstrated [10]. Further studies on AP-7 as a drug carrier in rats revealed liposomes containing AP-7 to be harmless to the experimental animals [15]. AP-7 containing liposomes did not affect functions of the excretory and cardiovascular systems, nor renal morphology [16]. These encouraging results are a good starting point for developing new, safe and efficient formulas of gene delivery.


Prenyl Ammonium Salts--New Carriers for Gene Delivery: A B16-F10 Mouse Melanoma Model.

Grecka E, Statkiewicz M, Gorska A, Biernacka M, Grygorowicz MA, Masnyk M, Chmielewski M, Gawarecka K, Chojnacki T, Swiezewska E, Malecki M - PLoS ONE (2016)

Structure of Amino-Prenols, the AP molecule contains an polyisoprenoid chain composed of n isoprene residues.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835110&req=5

pone.0153633.g001: Structure of Amino-Prenols, the AP molecule contains an polyisoprenoid chain composed of n isoprene residues.
Mentions: Polyprenyltrimethylammonium iodides, further called Amino-Prenols (APs) are cationic, semi-synthetic derivatives of polyprenols (Fig 1) [10]. Polyprenols are common constituents of plant photosynthetic tissues (for review see [11]). Together with dolichols, typically found in mammalian tissues, they constitute a group of polyisoprenoid lipids. Besides their role as cofactors in protein glycosylation and prenylation [12] polyisoprenoid alcohols are postulated to act as membrane fluidizers, fusiogenic agents [13] and components of the intracellular protein-transporting machinery [14]. Taking into account their fusogenic activity a concept of the feasibility of cationic derivatives of polyprenol as components of lipofecting formula was proposed and appropriate studies have been initiated. As a result good efficacy of in vitro transfection with application of AP-7-based (aminoprenol composed of seven isoprene units) complexes has been demonstrated [10]. Further studies on AP-7 as a drug carrier in rats revealed liposomes containing AP-7 to be harmless to the experimental animals [15]. AP-7 containing liposomes did not affect functions of the excretory and cardiovascular systems, nor renal morphology [16]. These encouraging results are a good starting point for developing new, safe and efficient formulas of gene delivery.

Bottom Line: AP-15/DOPE complexes were also efficient to introduce pDNA to cells, without much effect on cell viability.Furthermore, complexes containing AP-15 and therapeutic plasmid, encoding the TIMP metallopeptidase inhibitor 2 (TIMP2), introduced the TIMP2 gene with high efficiency to B16-F10 melanoma cells but not to B16-F10 melanoma tumors in C57BL/6 mice, as confirmed by TIMP2 protein level determination.Obtained results indicate that APs have a potential as non-viral vectors for cell transfection.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.

ABSTRACT

Purpose: Prenyl ammonium iodides (Amino-Prenols, APs), semi-synthetic polyprenol derivatives were studied as prospective novel gene transfer agents.

Methods: AP-7, -8, -11 and -15 (aminoprenols composed of 7, 8, 11 or 15 isoprene units, respectively) were examined for their capacity to form complexes with pDNA, for cytotoxicity and ability to transfect genes to cells.

Results: All the carriers were able to complex DNA. The highest, comparable to commercial reagents, transfection efficiency was observed for AP-15. Simultaneously, AP-15 exhibited the lowest negative impact on cell viability and proliferation--considerably lower than that of commercial agents. AP-15/DOPE complexes were also efficient to introduce pDNA to cells, without much effect on cell viability. Transfection with AP-15/DOPE complexes influenced the expression of a very few among 44 tested genes involved in cellular lipid metabolism. Furthermore, complexes containing AP-15 and therapeutic plasmid, encoding the TIMP metallopeptidase inhibitor 2 (TIMP2), introduced the TIMP2 gene with high efficiency to B16-F10 melanoma cells but not to B16-F10 melanoma tumors in C57BL/6 mice, as confirmed by TIMP2 protein level determination.

Conclusion: Obtained results indicate that APs have a potential as non-viral vectors for cell transfection.

No MeSH data available.


Related in: MedlinePlus