Paromomycin and neomycin B derived cationic lipids: Synthesis and transfection studies

Mével, Mathieu; Sainlos, Matthieu; Chatin, Benoît; Oudrhiri, Noufϊssa; Hauchecorne, Michèle; Lambert, Olivier; Vigneron, Jean‐Pierre; Lehn, Pierre; Pitard, Bruno; Lehn, Jean‐Maríe

doi:10.1016/j.jconrel.2011.12.019

Cited by 32 publications

(33 citation statements)

References 43 publications

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“…Kanamycin, an aminoglycoside antibiotic, potentiates the antibacterial effect of gold nanoparticles [25], therefore, kanamycin-capped gold particles were produced through a simple, biofriendly reaction to yield stable and monodispersed particles. These lipidic aminoglycoside derivatives are known to deliver siRNA and yield efficient gene silencing [26] as well as other nucleic acids [27,28].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…After 3 consecutive additions of MeOH and subsequent evaporations, the residue was purified by flash chromatography (reverse phase, C18-Silica, H 2 O+0.05 %TFA/MeOH) and lyophilized to give CholK (0.370 g, 61 %). 1 4 then linked to 4-(Dioleylamino)-4-oxobutanoic Acid to produce N,N Dioleyl-succinamide-Kanamycin-Teoc 3 followed by Teoc deprotection and purification, according to procedures extensively described in [27,28,63].…”

Section: Preparation Of Cholk and Doskmentioning

confidence: 99%

“…To prepare DosK reported in [21] the same procedure was followed as that of CholK except that the coupling of compound #4 with Cholesteryl Chloroformate was replaced by N-Succinyl-dioleylamine according to procedure extensively described in [27,28,63].…”

Section: Synthesis Of Cholk and Doskmentioning

confidence: 99%

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Unifying in vitro and in vivo IVT mRNA expression discrepancies in skeletal muscle via mechanotransduction

et al. 2018

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The translational efficiency of an in vitro transcribed (IVT) mRNA was measured upon delivery to primary skeletal muscle cells and to a mouse model system, towards the development of a predictive in vitro assay for the screening and validation of intramuscular mRNA-based vaccines. When IVT mRNA was delivered either naked or complexed with novel aminoglycoside-based delivery vehicles, significant differences in protein expression in vitro and in vivo were observed. We hypothesized that this previously anticipated discrepancy was due to differences in the mechanism of IVT mRNA endosomal entry and release following delivery. To address this, IVT mRNA was fluorescently labeled prior to delivery, to visualize its distribution. Colocalization with endosomal markers indicated that different entry pathways were utilized in vivo and in vitro, depending on the delivery vehicle, resulting in variations in protein expression levels. Since extracellular matrix stiffness (ECM) influences mRNA entry, trafficking and release, the effect of mechanotransduction on mRNA expression was investigated in vitro upon delivery of IVT mRNA alone, and complexed with delivery vehicles to skeletal muscle cells grown on ∼10 kPa hydrogels. This in vitro hydrogel model more accurately recapitulated the results obtained in vivo upon IM injection, indicating that this approach may assist in the characterization of mRNA based vaccines.

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Section: Accepted Manuscriptmentioning

confidence: 99%

Section: Preparation Of Cholk and Doskmentioning

confidence: 99%

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Unifying in vitro and in vivo IVT mRNA expression discrepancies in skeletal muscle via mechanotransduction

et al. 2018

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“…AG conjugates to an efflux pump inhibitor or to an antibiotic drug of another class (antibiotic hybrids) can promote, as adjuvants, the uptake of antibiotics through the OM of Gram-negative bacteria via the self-promoted uptake mechanism by displacement of the divalent cations (Ca 2+ or Mg 2+ ), which stabilize LPS [ 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 ]. The high affinity of strongly lipophilic AAGs of the first and second types for nucleic acids was used to develop efficient non-antibacterial vehicles for nucleic acid uptake in mammalian cells [ 129 , 130 , 131 , 132 , 133 , 134 , 135 ]. AAGs have also been employed for drug delivery [ 158 , 159 ] and their cationic characters should be exploited to deliver anionic drugs.…”

Section: Discussionmentioning

confidence: 99%

“…Amphiphilic TOB, KANA, PARO, NEO and NEA derivatives were demonstrated to be efficient intracellular delivery vehicles for biologically relevant molecules such as genes [ 130 , 131 , 132 , 133 , 134 ] and small interfering RNA (siRNA) [ 135 ]. The transfection potential of KANA and of its tri-guanidinylated derivative, conjugated to cholesterol through the formation of a carbamate group, was explored [ 130 , 131 , 132 ].…”

Section: Other Biological Activities Of Aagsmentioning

confidence: 99%

Amphiphilic Aminoglycosides as Medicinal Agents

Dezanet

Kempf

Mingeot‐Leclercq

et al. 2020

IJMS

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The conjugation of hydrophobic group(s) to the polycationic hydrophilic core of the antibiotic drugs aminoglycosides (AGs), targeting ribosomal RNA, has led to the development of amphiphilic aminoglycosides (AAGs). These drugs exhibit numerous biological effects, including good antibacterial effects against susceptible and multidrug-resistant bacteria due to the targeting of bacterial membranes. In the first part of this review, we summarize our work in identifying and developing broad-spectrum antibacterial AAGs that constitute a new class of antibiotic agents acting on bacterial membranes. The target-shift strongly improves antibiotic activity against bacterial strains that are resistant to the parent AG drugs and to antibiotic drugs of other classes, and renders the emergence of resistant Pseudomonas aeruginosa strains highly difficult. Structure–activity and structure–eukaryotic cytotoxicity relationships, specificity and barriers that need to be crossed in their development as antibacterial agents are delineated, with a focus on their targets in membranes, lipopolysaccharides (LPS) and cardiolipin (CL), and the corresponding mode of action against Gram-negative bacteria. At the end of the first part, we summarize the other recent advances in the field of antibacterial AAGs, mainly published since 2016, with an emphasis on the emerging AAGs which are made of an AG core conjugated to an adjuvant or an antibiotic drug of another class (antibiotic hybrids). In the second part, we briefly illustrate other biological and biochemical effects of AAGs, i.e., their antifungal activity, their use as delivery vehicles of nucleic acids, of short peptide (polyamide) nucleic acids (PNAs) and of drugs, as well as their ability to cleave DNA at abasic sites and to inhibit the functioning of connexin hemichannels. Finally, we discuss some aspects of structure–activity relationships in order to explain and improve the target selectivity of AAGs.

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Intracellular Antibody Delivery Mediated by Lipids, Polymers, and Inorganic Nanomaterials for Therapeutic Applications

et al. 2020

Advanced Therapeutics

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Therapeutic antibodies, due to their high affinity and specificity toward their biological targets, may demonstrate reduced harmful side effects compared with traditional drug moieties. While most of the as-yet clinically approved antibody therapeutics have targeted extracellular or membrane-bound domains, the ability to target intracellular antigens with antibodies opens up tremendous opportunities for imaging, diagnosis, and therapeutic applications. Generally, delivery concerns have limited the ability to target intracellular antigens, as many antibodies cannot easily cross the cell membrane due to their size and surface chemistry. Delivery platforms have been explored to address this issue, including physical methods, fusion protein/peptide techniques, and synthetic carrier-based systems. This review summarizes the progress of carrier-based intracellular antibody delivery systems employing synthetic lipids, polymers, and inorganic nanomaterials. Antibodies targeting various epitopes have been loaded through adsorption, conjugation, or physical encapsulation strategies. Successful intracellular deliveries have been demonstrated largely through fluorescence imaging using dye-labeled antibody cargos. Specific synthetic delivery platforms have great potential for ex vivo and in vivo therapeutic applications. Challenges and opportunities are further discussed for material scientists to explore in this research area.

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Paromomycin and neomycin B derived cationic lipids: Synthesis and transfection studies

Cited by 32 publications

References 43 publications

Unifying in vitro and in vivo IVT mRNA expression discrepancies in skeletal muscle via mechanotransduction

Unifying in vitro and in vivo IVT mRNA expression discrepancies in skeletal muscle via mechanotransduction

Amphiphilic Aminoglycosides as Medicinal Agents

Intracellular Antibody Delivery Mediated by Lipids, Polymers, and Inorganic Nanomaterials for Therapeutic Applications

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