Cationic β-cyclodextrin bilayer vesicles

Donohue, Ruth; Mazzaglia, Antonino; Ravoo, Bart Jan; Darcy, Raphael

doi:10.1039/b207238f

Cited by 95 publications

(86 citation statements)

References 26 publications

(8 reference statements)

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“…25 Briefly, β-CD was substituted on the primary side with lipophilic chains (C 12 ) by thioalkylation. 18,26 Introduction of amphiphilic moieties improves the transfection efficiency of cationic CDs. 18,22 Functionalization at the 2-position was by means of a copper-catalyzed "click" reaction, which represents an efficient and versatile strategy for modifying the secondary side with diverse groups, including cationic groups and polyethyleneglycol (PEG) chains.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Click-Modified Cyclodextrins as Nonviral Vectors for Neuronal siRNA Delivery

O’Mahony

Godinho

Ogier

et al. 2012

ACS Chem. Neurosci.

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RNA interference (RNAi) holds great promise as a strategy to further our understanding of gene function in the central nervous system (CNS) and as a therapeutic approach for neurological and neurodegenerative diseases. However, the potential for its use is hampered by the lack of siRNA delivery vectors which are both safe and highly efficient. Cyclodextrins have been shown to be efficient and low toxicity gene delivery vectors in various cell types in vitro. However, to date, they have not been exploited for delivery of oligonucleotides to neurons. To this end, a modified β-cyclodextrin (CD) vector was synthesized, which complexed siRNA to form cationic nanoparticles of less than 200 nm in size. Furthermore, it conferred stability in serum to the siRNA cargo. The in vitro performance of the CD in both immortalized hypothalamic neurons and primary hippocampal neurons was evaluated. The CD facilitated high levels of intracellular delivery of labeled siRNA, while maintaining at least 80% cell viability. Significant gene knockdown was achieved, with a reduction in luciferase expression of up to 68% and a reduction in endogenous glyceraldehyde phosphate dehydrogenase (GAPDH) expression of up to 40%. To our knowledge, this is the first time that a modified CD has been used as a safe and efficacious vector for siRNA delivery into neuronal cells.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Click-Modified Cyclodextrins as Nonviral Vectors for Neuronal siRNA Delivery

O’Mahony

Godinho

Ogier

et al. 2012

ACS Chem. Neurosci.

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“…The same authors reported the first examples of polycationic amphiphilic CDs by converting the terminal hydroxyls to amino groups through iodination (!30), azide substitution (!31), and reduction (!32). [65] These compounds were shown to entrap pDNA by forming nanoparticles that behaved similarly to Lipofectamine -derived lipoplexes in terms of transfection efficiency and toxicity against COS-7 and Hep G2 cells. [66] The authors correlated the gene-delivery capability of the vectors with the length of the hydrocarbon chain.…”

Section: Polycationic Cyclodextrins-pdna Complexes (Cdplexes)mentioning

confidence: 99%

Preorganized, Macromolecular, Gene‐Delivery Systems

Mellet

Benito

Fernández

2010

Chemistry A European J

115

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Viruses represent a paradigmatic example of multicomponent, self‐organized supramolecular systems specialized in the delivery and replication of their genetic material. Mimicking their functioning by artificial synthetic molecules represents a fantastic challenge that will lead to the future development of gene therapy. This is only possible if general approaches towards the construction of nanoscale vehicles for DNA are developed and the key rules governing their capacity to compact genetic material and its active transport/delivery through cell membranes are understood. In this area of research, synthetic organic chemistry plays an important role by providing tools to create tailor‐made molecules of increasing complexity. Preorganization of functional elements onto macromolecular platforms has the potential to allow control of the self‐assembling behavior of discrete architectures to produce nanometric objects that can be programmed to complex, compact, deliver, and release plasmid DNA in a target cell.

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“…This is not typical when compared to the other CD-based gene delivery vectors studied by our group (Cryan et al, 2004b; and is likely to be influencing the hydrophilic-hydrophobic balance within this CD. Changing the hydrophilic-hydrophobic balance can result in differences in the type of self-assembled complexes formed with amphiphilic CDs (Donohue et al, 2002), which may in turn affect uptake and transfection, as has been the case for lipoplexes (Ma et al, 2007).…”

Section: Discussionmentioning

confidence: 99%