Lysine-based amino-functionalized lipids for gene transfection: 3D phase behaviour and transfection performance

Tassler, Stephanie; Pawlowska, Dorota; Janich, Christopher; Giselbrecht, Julia; Drescher, Simon; Langner, Andreas; Wölk, Christian; Brezesinski, Gerald

doi:10.1039/c8cp01922c

Cited by 10 publications

(15 citation statements)

References 46 publications

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“…7 E) [ 48 ]. The presented cell adhesion studies underline the beneficial effect of Col I as the terminal surface layer but also that the adsorbed liposomes possess an excellent biocompatibility as found in our previous studies [ 27 , 28 ].…”

Section: Resultssupporting

confidence: 78%

“…The addition of cationic liposome, LbL sequence [CS, Col I] 4 -CS-Lip, results in a PZC at higher pH values (around pH 6) due to the primary amino functions in the head group. In a previous work the pKa of OO4 was determined at pH 6 [ 27 ], this means that more than 99% of the lipid species are uncharged at pH ≈ 8. The observed shift in the PZC also supports that liposomes were irreversibly adsorbed on the surface and do not desorbing during the washing steps with NaCl.…”

Section: Resultsmentioning

confidence: 99%

“…Malonic acid diamides are a group of peptide-mimicking cationic lipids, which are useful components to formulate liposomes with a positive surface charge, low cytotoxicity, and extremely high transfection efficiency [ 27 , 28 ]. These cationic liposomes can potentially be embedded in multilayer films based on LbL to retain these lipid containers after the localized release of a bioactive compound or alternatively, release the entire container with functional cargos from surfaces into the cells or surrounding tissue [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

“…

Fig. 1 A) Schematic illustration of the preparation of liposomes using the cationic lipid OO4 and the zwitterionic co-lipid DOPE (protonation state at pH 4) [ 27 ]. The liposomes can be used as a carrier for hydrophilic and lipophilic drugs.…”

Section: Introductionmentioning

confidence: 99%

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Engineering osteogenic microenvironments by combination of multilayers from collagen type I and chondroitin sulfate with novel cationic liposomes

Barrera

Hause

Menzel

et al. 2020

Materials Today Bio

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Cationic liposomes composed of a novel lipid (N-{6-amino-1-[N-(9Z) -octadec9-enylamino] -1-oxohexan-(2S) -2-yl} –N’- {2- [N, N-bis(2-aminoethyl) amino] ethyl} -2-hexadecylpropandiamide) (OO4) and dioleoylphosphatidylethanolamine (DOPE) possess high amounts of amino groups and are promising systems for lipofection. Moreover, these cationic liposomes can also be used as a polycationic entity in multilayer formation using layer-by-layer technique (LbL), which is a method to fabricate surface coatings by alternating adsorption of polyanions and polycations. Since liposomes are suitable for endocytosis by or fusion with cells, controlled release of their cargo on site is possible. Here, a polyelectrolyte multilayer (PEM) system was designed of chondroitin sulfate (CS) and collagen type I (Col I) by LbL technique with OO4/DOPE liposomes embedded in the terminal layers to create an osteogenic microenvironment. Both, the composition of PEM and cargo of the liposomes were used to promote osteogenic differentiation of C2C12 myoblasts as in vitro model. The internalization of cargo-loaded liposomes from the PEM into C2C12 cells was studied using lipophilic (Rhodamine-DOPE conjugate) and hydrophilic (Texas Red–labeled dextran) model compounds. Besides, the use of Col I and CS should mimic the extracellular matrix of bone for future applications such as bone replacement therapies. Physicochemical studies of PEM were done to characterize the layer growth, thickness, and topography. The adhesion of myoblast cells was also evaluated whereby the benefit of a cover layer of CS and finally Col I above the liposome layer was demonstrated. As proof of concept, OO4/DOPE liposomes were loaded with dexamethasone, a compound that can induce osteogenic differentiation. A successful induction of osteogenic differentiation of C2C12 cells with the novel designed liposome-loaded PEM system was shown. These findings indicate that designed OH4/DOPE loaded PEMs have a high potential to be used as drug delivery or transfection system for implant coating in the field of bone regeneration and other applications.

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Section: Resultssupporting

confidence: 78%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…

Section: Introductionmentioning

confidence: 99%

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Engineering osteogenic microenvironments by combination of multilayers from collagen type I and chondroitin sulfate with novel cationic liposomes

Barrera

Hause

Menzel

et al. 2020

Materials Today Bio

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“…50 Nevertheless, recently, we demonstrated that a lipoplex formulation with a lamellar superstructure was more efficient than a lipoplex with a cubic structure. 51 Obviously, more factors (for instance lipoplex stability, lipoplex charge, and binding strength between lipids and DNA) than the fusiogenic potential of cubic phases affect the transfection efficiency.…”

mentioning

confidence: 99%

Interactions of Cationic Lipids with DNA: A Structural Approach

Dittrich

Brauer

Funari³

et al. 2018

Langmuir

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Colloidal nucleic acid carrier systems based on cationic lipids are a promising pharmaceutical tool in the implementation of gene therapeutic strategies. This study demonstrates the complex behavior of DNA at the lipid-solvent interface facilitating structural changes of the lyotropic liquid-crystalline phases. For this study, the structural properties of six malonic acid based cationic lipids were determined using small- and wide-angle X-ray scattering (SAXS and WAXS) as well as differential scanning calorimetry (DSC). Selected lipids (lipid 3 and lipid 6) with high nucleic acid transfer activity have been investigated in detail because of the strong influence of the zwitterionic helper lipid 1,2-di(9 Z-octadecenoyl)- sn-glycero-3-phosphoethanolamine (DOPE) on the structural properties as well as of the complex formation of lipid-DNA complexes (lipoplexes). In the case of lipid 3, DNA stabilizes a metastable cubic mesophase with Im3 m symmetry and an Im3 m Q lipoplex is formed, which is rarely described for DNA lipoplexes in literature. In the case of lipid 6, a cubic mesophase with Im3 m symmetry turns into a fluid lamellar phase while mixing with DOPE and complexing DNA.

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Investigating 3R In Vivo Approaches for Bio‐Distribution and Efficacy Evaluation of Nucleic Acid Nanocarriers: Studies on Peptide‐Mimicking Ionizable Lipid

Giselbrecht

Pinnapireddy

Alioglu

et al. 2022

Small

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Formulations based on ionizable amino‐lipids have been put into focus as nucleic acid delivery systems. Recently, the in vitro efficacy of the lipid formulation OH4:DOPE has been explored. However, in vitro performance of nanomedicines cannot correctly predict in vivo efficacy, thereby considerably limiting pre‐clinical translation. This is further exacerbated by limited access to mammalian models. The present work proposes to close this gap by investigating in vivo nucleic acid delivery within simpler models, but which still offers physiologically complex environments and also adheres to the 3R guidelines (replace/reduce/refine) to improve animal experiments. The efficacy of OH4:DOPE as a delivery system for nucleic acids is demonstrated using in vivo approaches. It is shown that the formulation is able to transfect complex tissues using the chicken chorioallantoic membrane model. The efficacy of DNA and mRNA lipoplexes is tested extensively in the zebra fish (Danio rerio) embryo which allows the screening of biodistribution and transfection efficiency. Effective transfection of blood vessel endothelial cells is seen, especially in the endocardium. Both model systems allow an efficacy screening according to the 3R guidelines bypassing the in vitro–in vivo gap. Pilot studies in mice are performed to correlate the efficacy of in vivo transfection.

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Lysine-based amino-functionalized lipids for gene transfection: 3D phase behaviour and transfection performance

Cited by 10 publications

References 46 publications

Engineering osteogenic microenvironments by combination of multilayers from collagen type I and chondroitin sulfate with novel cationic liposomes

Engineering osteogenic microenvironments by combination of multilayers from collagen type I and chondroitin sulfate with novel cationic liposomes

Interactions of Cationic Lipids with DNA: A Structural Approach

Investigating 3R In Vivo Approaches for Bio‐Distribution and Efficacy Evaluation of Nucleic Acid Nanocarriers: Studies on Peptide‐Mimicking Ionizable Lipid

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