Neutral Postgrafted Colloidal Particles for Gene Delivery

Thompson, Betty J.; Mignet, Nathalie; Hofland, Hans; Lamons, D.; Séguin, Johanne; Nicolazzi, Céline; Figuera, Natalia de la; Kuen, René Lai; Meng, Xianguang; Scherman, Daniel; Bessodes, Michel

doi:10.1021/bc040244z

Cited by 46 publications

(38 citation statements)

References 14 publications

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“…However, the positive charges of the cationic lipids induce a poor efficiency in vivo [3], [4] as lipoplexes are captured by opsonins or other physiological components, hence resulting in a low circulation time [5]. Numerous studies have been undertaken to improve serum resistance by masking or suppressing the cationic charges [6], [7]. Alternative delivery systems have been introduced, using non electrostatic interaction with DNA.…”

Section: Introductionmentioning

confidence: 99%

Iminothiol/thiourea tautomeric equilibrium in thiourea lipids impacts DNA compaction by inducing a cationic nucleation for complex assembly

Breton¹,

Bessodes²,

Bouaziz³

et al. 2009

Biophysical Chemistry

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT2 Abstract: Our research on lipidic vectors for transfection led us to develop thiourea lipids able to interact with DNA. Hence, we developed a series of lipopolythioureas based on the strong hydrogen bond donor ability of thiourea. More recently we have reported a branched hydroxylated bis-thiourea derivative with interesting transfecting properties. The last step of the syntheses involved a strong acidic condition, leading to an unstable product upon storage.Therefore we designed a new synthesis in mild acidic conditions. Though they exhibit the same mass, the lipids obtained in the two different conditions differ by their interaction with DNA. We therefore explored the physicochemical properties of these two lipids by different means that we describe in this article. In order to insure easier and reliable 13 C-NMR studies of the thiourea group we have designed the synthesis of the corresponding 13 C-labelled thiourea lipids. We have thus shown that when the lipid was submitted to mildly acidic medium; only the thiourea group was observed; while a thiourea/charged and/or uncharged iminothiol tautomeric equilibrium formed when the last step of the synthesis was submitted to low pH. NMR experiments showed that this tautomeric equilibrium could not form in polar solvents. However, UV experiments on the liposomal form of the lipopolythiourea showed the presence of the tautomers. Lipid/DNA interaction consequently differed according to the acidic treatment applied. Eventually, these results revealed that on this particular thiourea lipid, electrostatic interactions due to cationic thioureas are likely to be responsible for DNA compaction and that this tautomeric form of the thiourea could be stabilised by hydrogen bonds in a supramolecular assembly. Nevertheless, this does not reflect a general thiourea lipid/DNA interaction as other thiourea lipids that are able to compact DNA do not undergo an acidic treatment during the final stage of their synthesis.

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Section: Introductionmentioning

confidence: 99%

Iminothiol/thiourea tautomeric equilibrium in thiourea lipids impacts DNA compaction by inducing a cationic nucleation for complex assembly

Breton¹,

Bessodes²,

Bouaziz³

et al. 2009

Biophysical Chemistry

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“…Therefore, the second strategy involves the covalent attachment of the shielding polymer to preformed non-viral nanocomplexes [88]. Since PEGylation may prevent endosomal escape, different groups are currently developing several strategies in which the nanocomplexes are deprived of their PEG-chains outside the cellor in acidifying endosomal compartments [89].…”

Section: Pegylation As Methods For Shielding Nanocomplexesmentioning

confidence: 99%

Nanocomplexes for gene therapy of respiratory diseases: Targeting and overcoming the mucus barrier

Gioia

Trapani

Castellani

et al. 2015

Pulmonary Pharmacology & Therapeutics

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“…[23][24][25] This information suggested that the liposomal hydration level is another important factor affecting its association with the cell membrane. Here we examined the effect of MEL-A and Tween 80 on hydration levels of liposomes and lipoplexes.…”

Section: The Hydration Level Of Liposomes and Lipoplexes As Monitoredmentioning

confidence: 97%

Surface Properties of Lipoplexes Modified with Mannosylerythritol Lipid-A and Tween 80 and Their Cellular Association

Ding

Hattori

et al. 2009

CHEMICAL & PHARMACEUTICAL BULLETIN

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For effective gene transfection into mammalian cells, numerous cationic lipids have been synthesized and formulated into cationic liposomes. [1][2][3] In general, the diverse cationic lipids contain a hydrophobic region, a linker and a cationic headgroup, which are substantially quite variable in different cationic lipids. However, in the cationic headgroup, the basic element is amine, which is responsible for DNA complexation as a protonized form. All four amine types, from primary to quaternary amine, have been reported in diverse cationic lipids and exhibited substantially different cellular association and gene transfection capabilities. 4,5) Understanding the key step in gene transfection, i.e. cellular association of lipoplexes, which is largely determined by the physiochemical properties of cationic liposomes and their lipoplexes, will provide valuable information for designing more effective cationic lipids and optimizing the liposomal formulation. Particle size and zeta potentials of lipoplexes are often reported when discussing their cellular association [6][7][8] ; however, another physiochemical property, the surface hydration of lipoplexes, is always neglected. Although the hydration levels of lipoplexes containing different liposomal formulations have been well established, 9-11) their effect on the cellular association of lipoplexes is still lacking.We reported previously that cationic liposomes, composed of dioleoylphosphatidylethanolamine (DOPE) and N,Nmethyl hydroxyethyl aminopropane carbamoyl cholesterol (MHAPC) or cholesteryl-3b-carboxyamindoethylene-N-hydroxyethylamine (OH-Chol), demonstrated distinctive differences in their cellular association and gene transfection efficiencies in vitro.12) The major differences between MHAPC and OH-Chol are the amine types and linkers shown in Fig. 1, with MHAPC having a tertiary amine linked to the cholesteryl skeleton by a carbamate ester, and OH-Chol having a secondary amine with an amido linker. To understand the different cellular association of lipoplexes composed of different cationic lipids, the effect of amine types and linkers on the surface properties, e.g. zeta potentials and surface hydration levels, was examined. Furthermore, mannosylerythritol lipid-A (MEL-A) is a newly developed biosurfactant 13) and modification of OH-Chol-liposomes with MEL-A markedly increased the gene transfection efficiency of plasmid DNA.14,15) Recent findings found that MEL-A induced membrane fusion between the target cells and cationic liposomes 16,17) ; however, the physiochemical mechanism of the fusion ability of MEL-A has not been fully understood. As a

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Neutral Postgrafted Colloidal Particles for Gene Delivery

Cited by 46 publications

References 14 publications

Iminothiol/thiourea tautomeric equilibrium in thiourea lipids impacts DNA compaction by inducing a cationic nucleation for complex assembly

Iminothiol/thiourea tautomeric equilibrium in thiourea lipids impacts DNA compaction by inducing a cationic nucleation for complex assembly

Nanocomplexes for gene therapy of respiratory diseases: Targeting and overcoming the mucus barrier

Surface Properties of Lipoplexes Modified with Mannosylerythritol Lipid-A and Tween 80 and Their Cellular Association

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