Relationships between the physicochemical properties of an amphiphilic triblock copolymers/DNA complexes and their intramuscular transfection efficiency

Bello-Roufai, Mahajoub; Lambert, Olivier; Pitard, Bruno

doi:10.1093/nar/gkl860

Cited by 40 publications

(41 citation statements)

References 41 publications

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“…These results are comparable with some of the research carried out with pluronics block copolymers, which have been, and continue to be, extensively explored. 34,42,43 Similar to these, as well as to other vehicles, in vitro transfection activity of lipospermines was poor (data not shown). 38,42 Delivery systems that are efficient in the skeletal muscle or skin may be used for the purpose of DNA vaccine development.…”

Section: Discussionsupporting

confidence: 66%

“…Previous studies with a chemically different set of spermine derivatives used for DNA condensation have shown the formation of complexes, but not as well defined or with as regular a shape as some of the DNA particles shown in this investigation, particularly with decanoylspermine/DNA. 18,34 Influence of imaging techniques on morphological characterization of DNA complexes does not seem to be uncommon and cryo-EM emerges as that which may interfere the least. [24][25][26][27]35 The morphology of these lipospermines is likely to influence their in vivo transfection efficiency, but the correlation is not clear.…”

Section: Discussionmentioning

confidence: 99%

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Fatty acid–spermine conjugates as DNA carriers for nonviral in vivo gene delivery

et al. 2009

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The lack of efficient in vivo gene delivery is a well-known shortcoming of nonviral delivery vectors, in particular of chemical vectors. We developed a series of novel nonviral carriers for plasmid-based in vivo gene delivery. This new transport device is based on the assembly of DNA plasmids with synthetic derivatives of naturally occurring moleculesfatty acid-spermine conjugates (or lipospermines). We tested the ability of these fatty acid conjugates to interact with plasmid DNA (pDNA) and found that they formed DNA nanocomplexes, which are protected from DNase I degradation. This protection was shown to directly correlate with the length of the aliphatic component. However, this increase in the length of the hydrocarbon chain resulted in increased toxicity. The cationic lipids used for transfection typically have a C 16 and C 18 hydrocarbon chain. Interestingly, toxicity studies, together with further characterization studies, suggested that the two most suitable candidates for in vivo delivery are those with the shortest hydrocarbon chain, butanoyl-and decanoylspermine. Morphological characterization of DNA nanocomplexes resulting from these lipospermines showed the formation of a homogenous population, with the diameter ranging approximately from 40 to 200 nm. Butanoylspermine was found to be the most promising carrier from this series, resulting in a significantly increased gene expression, in relation to naked plasmid, in both tissues herein targeted (dermis and M. tibialis anterior). Thus, we established a correlation between the in vitro properties of the ensuing DNA nanocarriers and their efficient in vivo gene expression.

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Section: Discussionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Fatty acid–spermine conjugates as DNA carriers for nonviral in vivo gene delivery

et al. 2009

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“…4,5 It has been shown that PEG induces significant changes in DNA solubility and structure under given conditions. 6 DNA concentration, pH, ionic strength of the solution, and the presence of divalent metal ions have been shown to impact PEG-DNA precipitation. 6 PEGylation of synthetic polymers such as dendrimers is shown to reduce toxicity and increase biocompatibility and DNA transfection.…”

Section: ■ Introductionmentioning

confidence: 99%

Effect of PEG and mPEG-Anthracene on tRNA Aggregation and Particle Formation

et al. 2011

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Poly(ethylene glycol) (PEG) and its derivatives are synthetic polymers with major applications in gene and drug delivery systems. Synthetic polymers are also used to transport miRNA and siRNA in vitro. We studied the interaction of tRNA with several PEGs of different compositions, such as PEG 3350, PEG 6000, and mPEG-anthracene under physiological conditions. FTIR, UV−visible, CD, and fluorescence spectroscopic methods as well as atomic force microscopy (AFM) were used to analyze the PEG binding mode, the binding constant, and the effects of polymer complexation on tRNA stability, aggregation, and particle formation. Structural analysis showed that PEG-tRNA interaction occurs via RNA bases and the backbone phosphate group with both hydrophilic and hydrophobic contacts. The overall binding constants of K PEG 3350-tRNA = 1.9 (±0.5) × 10 4 M −1 , K PEG 6000-tRNA = 8.9 (±1) × 10 4 M −1 , and K mPEG-anthracene = 1.2 (±0.40) × 10 3 M −1 show stronger polymer− RNA complexation by PEG 6000 and by PEG 3350 than the mPEG-anthracene. AFM imaging showed that PEG complexes contain on average one tRNA with PEG 3350, five tRNA with PEG 6000, and ten tRNA molecules with mPEGanthracene. tRNA aggregation and particle formation occurred at high polymer concentrations, whereas it remains in A-family structure. ■ INTRODUCTIONSynthetic polymers play a major role in drug and gene delivery.1−3 Among synthetic polymers, poly(ethylene glycol) and its derivatives show potential applications in gene and drug delivery due to their solubility, nontoxicity, and biocompatibility. 4,5 It has been shown that PEG induces significant changes in DNA solubility and structure under given conditions. 6 DNA concentration, pH, ionic strength of the solution, and the presence of divalent metal ions have been shown to impact PEG-DNA precipitation.6 PEGylation of synthetic polymers such as dendrimers is shown to reduce toxicity and increase biocompatibility and DNA transfection. 4,5,7 Similarly, the effect of PEGylation on the toxicity and permeability of biopolymers such as chitosan has been recently reported. 8,9 Whereas major attention has been focused on polymer−DNA complexes because of their applications in gene delivery, little is known about polymer−RNA interaction. Synthetic polymers can transport miRNA and siRNA in vitro.10−12 The interaction of dendrimers with tRNA has been recently reported. 13 Even though the interactions of PEGylated dendrimers with DNA, RNA, and protein are wellcharacterized, 13−16 detailed structural analysis of PEG and mPEG derivatives complexes with RNA is not known. Therefore, it was of interest to study the interaction of PEGs and mPEGderivatives with tRNA, using spectroscopic methods and AFM imaging.Fluorescence quenching has been used as a technique for quantifying the binding affinities of macromolecules with ligands. 17Fluorescence quenching is the decrease of the quantum yield of fluorescence from a fluorophore, induced by a variety of molecular interactions with quencher molecule. Therefore, it is possibl...

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“…Dendrimers (Scheme 1) are also unique synthetic macromolecules of nanometer dimensions with a highly branched structure and globular shape with strong affinity towards DNA and RNA complexation [4][5][6][7][8][9][10]. It has been shown that synthetic polymers induce significant changes in DNA and RNA solubility and structure under given conditions [8][9][10][11][12][13][14][15][16][17][18][19][20]. Synthetic polymers are also used to transport miRNA and siRNA in vitro [11][12][13][14][15][16][17][18][19][20][21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

“…It has been shown that synthetic polymers induce significant changes in DNA and RNA solubility and structure under given conditions [8][9][10][11][12][13][14][15][16][17][18][19][20]. Synthetic polymers are also used to transport miRNA and siRNA in vitro [11][12][13][14][15][16][17][18][19][20][21][22][23][24]. PEGylation of synthetic polymers such as dendrimers is shown to reduce toxicity and increase biocompatibility and DNA Transfection [6,7,9].…”

Section: Introductionmentioning

confidence: 99%

Effect of Synthetic Polymers on tRNA Nanoparticle Formation

HA¹

2015

JNMR

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In this review, we have examined the effects of several synthetic nanoparticles such as poly (ethylene glycol) PEG-(PEG-3350, PEG-6000), methoxypoly (ethylene glycol) anthracene (mPEG-anthracene), methoxypoly (ethylene glycol) poly (amidoamine) (mPEG-PAMAM-G3), (mPEG-PAMAM-G4) and poly (amidoamine) (PAMAM-G4) on tRNA structure and dynamics. Atomic force microscopic (AFM) images and spectroscopic data were analysed and the effects of synthetic polymer complexation on tRNA stability, aggregation and particle formation are discussed. Hydrophilic and hydrophobic contacts were dominated in the polymer-tRNA complexation and the overall binding constants showed that the order of binding is PEG-6000>PAMAM-G4>PEG-3350>mPEG-PAMAM-G4>mPEG-PAMAM-G3>mPEG-anthracene. The morphology of polymer-tRNA complexes showed major aggregation and nanoparticle formation of tRNA, in the presence of synthetic nanoparticles.

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Relationships between the physicochemical properties of an amphiphilic triblock copolymers/DNA complexes and their intramuscular transfection efficiency

Cited by 40 publications

References 41 publications

Fatty acid–spermine conjugates as DNA carriers for nonviral in vivo gene delivery

Fatty acid–spermine conjugates as DNA carriers for nonviral in vivo gene delivery

Effect of PEG and mPEG-Anthracene on tRNA Aggregation and Particle Formation

Effect of Synthetic Polymers on tRNA Nanoparticle Formation

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