Cyclen-based double-tailed lipids for DNA delivery: Synthesis and the effect of linking group structures

Zhang, Yimei; Chang, De-Chun; Zhang, Ji; Liu, Yanhong; Yu, Xiao‐Qi

doi:10.1016/j.bmc.2015.07.005

Cited by 13 publications

(2 citation statements)

References 27 publications

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“…In addition, the unique macrocyclic polyamine structure endows cyclen with an excellent metal coordination ability . Therefore, cyclen has become a good structural candidate for the design of non-viral gene vectors. − However, most of cyclen-based cationic lipids exhibited lower transfection efficiency (TE) and higher cytotoxicity compared with Lipofectamine 2000 (Lipo). Recently, it was found that the coordination of Zn(II) toward a dipicolylamine moiety could dramatically increase the TE and reduce cytotoxicity, shedding light on the design of gene vectors involving cyclen, which may also well coordinate to Zn ions .…”

Section: Introductionmentioning

confidence: 99%

Liposomes Derived from Macrocyclic Polyamine as a Versatile Macromolecule Delivery System

Guo

Chen

Yang

et al. 2020

ACS Appl. Bio Mater.

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Macromolecular therapeutic agents such as nucleic acids and proteins have attracted increased attention due to the satisfactory specificity and potent therapeutic effect, holding great significance for the treatment of major and complicated diseases. Cationic lipids possess tremendous potential for the intercellular delivery of macromolecular agents, while their delivery efficiency and biocompatibility remain challenging. Herein, two 1,4,7,10-tetraazacyclododecane (cyclen)-based lipids and their Zn(II) complexes were prepared, and the formed liposomes were applied as versatile vectors for various macromolecular cargos including plasmid DNA, siRNA, and proteins. It was found that high delivery efficiency toward different types of cargos could be achieved by simple adjustment of the lipid structure. Zn coordination could largely reduce the cytotoxicity of the delivery complexes, and the Zn(II)-coordinated single-tailed cyclen lipid exhibited much higher plasmid gene transfection efficiency than Lipofectamine 2000. Meanwhile, cyclen lipids with double fluorinated tails could give better performance in the delivery of siRNA. It was supposed that lipids with a relatively lower nucleic acid condensation ability might release the cargo more easily in the cytoplasm, resulting in weaker DNA transfection and better siRNA gene silencing. Moreover, the double-tailed lipid could also efficiently transfer special proteins into cells without function loss. These results show the promise of cyclen-based lipids in the application of nucleic acid and protein delivery and further biomacromolecule therapy.

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Section: Introductionmentioning

confidence: 99%

Liposomes Derived from Macrocyclic Polyamine as a Versatile Macromolecule Delivery System

Guo

Chen

Yang

et al. 2020

ACS Appl. Bio Mater.

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“…With a reliable method for Boc deprotection of 9 and subsequent isolation of 3 in hand, we shifted focus back to the acylation of the diol 4 . Although precedent exists for diacylation of related diols with carboxylic acids under modified peptide coupling conditions, we sought a simpler procedure. Initial attempts to develop a phase transfer catalyzed acylation with commercially available myristoyl chloride 5 showed excellent reactivity and selectivity for the desired product 9 .…”

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confidence: 99%

Crystallizing Fats? Development of a Scalable, Chromatography-Free Synthesis of Cationic Lipids

Beutner

Ayers

Brueggemeier

et al. 2020

Org. Process Res. Dev.

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Research on the development of scalable routes to pharmaceutical intermediates typically proceeds from explorations of the chemistry to the identification of robust procedures for isolation. Although this order of investigation works well for typical small molecules possessing favorable physical properties and, therefore, numerous options for isolation, this is not always the case. The synthesis of cationic lipids is an exception to the rule and challenges this logic. Supported by extensive solubility and salt screening, we engaged in a reverse development effort, focusing first on identifying isolation conditions and then using that information to select appropriate chemistry. This strategy allowed for development of a robust, chromatography-free route to the cationic lipids of interest that was implemented at kilogram scale with quantifiable improvements to yield and efficiency when compared to the original route.

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Derivatives of Macrocyclic Polyamines as Nanovector Materials

2017

Macrocyclic Polyamines

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Cyclen-based double-tailed lipids for DNA delivery: Synthesis and the effect of linking group structures

Cited by 13 publications

References 27 publications

Liposomes Derived from Macrocyclic Polyamine as a Versatile Macromolecule Delivery System

Liposomes Derived from Macrocyclic Polyamine as a Versatile Macromolecule Delivery System

Crystallizing Fats? Development of a Scalable, Chromatography-Free Synthesis of Cationic Lipids

Derivatives of Macrocyclic Polyamines as Nanovector Materials

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