Diol glycidyl ether-bridged cyclens: preparation and their applications in gene delivery

Yi, Wen-Jing; Feng, Zhi-Hua; Zhang, Qinfang; Zhang, Ji; Li, Ling-Dong; Zhu, Wen; Yu, Xiao‐Qi

doi:10.1039/c0ob00879f

Cited by 19 publications

(8 citation statements)

References 36 publications

(25 reference statements)

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“…For these reasons, the invention of new cargo systems that are efficient, economical, and easily synthesized and applied is of great interest. In addition to the established polymer‐ and lipid‐based nonviral transfection agents, some effective small molecular systems have been reported, for example, cyclodextrins and calixarenes, metal complexes, and cyclene derivatives . However, these molecules often require auxiliary agents such as the addition of helper lipids to perform well.…”

Section: Introductionmentioning

confidence: 99%

A Systematic Structure–Activity Study of a New Type of Small Peptidic Transfection Vector Reveals the Importance of a Special Oxo‐Anion‐Binding Motif for Gene Delivery

et al. 2017

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We discovered a new class of artificial peptidic transfection vectors based on an artificial anion-binding motif, the guanidiniocarbonylpyrrole (GCP) cation. This new type of vector is surprisingly smaller than traditional systems, and our previous work suggested that the GCP group was important for promoting critical endosomal escape. We now present here a systematic comparison of similar DNA ligands featuring our GCP oxo-anion-binding motif with DNA ligands only consisting of naturally occurring amino acids. Structure-activity studies showed that the artificial binding motif clearly outperformed natural amino acids such as histidine, lysine, and arginine. It improved the ability to shuttle foreign genetic material into cells, yet successfully mediated endosomal escape. Also, plasmids that were complexed by our artificial ligands were stabilized against cytosolic degradation to some extent. This resulted in the successful expression of plasmid information (comparable to gold standards such as polyethyleneimine). Hence, our study clearly demonstrates the importance of the tailor-made GCP anion-binding site for efficient gene transfection.

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Section: Introductionmentioning

confidence: 99%

A Systematic Structure–Activity Study of a New Type of Small Peptidic Transfection Vector Reveals the Importance of a Special Oxo‐Anion‐Binding Motif for Gene Delivery

et al. 2017

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“…To the best of our knowledge, there is no example using cyclic polyamines as the hydrophilic headgroup of cationic lipid for gene delivery. Our previous studies revealed that some 1, 4, 7, 10-tetraazacyclododecane (cyclen) based cationic lipids [19] or linear [20] and reticular [21] polymers, which could transfer plasmid DNA into cells without use of extraneous agent. However, the transfection efficiency (TE) was not satisfying.…”

Section: Introductionmentioning

confidence: 99%

Cyclen-Based Cationic Lipids for Highly Efficient Gene Delivery towards Tumor Cells

et al. 2011

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BackgroundGene therapy has tremendous potential for both inherited and acquired diseases. However, delivery problems limited their clinical application, and new gene delivery vehicles with low cytotoxicity and high transfection efficiency are greatly required.MethodsIn this report, we designed and synthesized three amphiphilic molecules (L1–L3) with the structures involving 1, 4, 7, 10-tetraazacyclododecane (cyclen), imidazolium and a hydrophobic dodecyl chain. Their interactions with plasmid DNA were studied via electrophoretic gel retardation assays, fluorescent quenching experiments, dynamic light scattering and transmission electron microscopy. The in vitro gene transfection assay and cytotoxicity assay were conducted in four cell lines.ResultsResults indicated that L1 and L3-formed liposomes could effectively bind to DNA to form well-shaped nanoparticles. Combining with neutral lipid DOPE, L3 was found with high efficiency in gene transfer in three tumor cell lines including A549, HepG2 and H460. The optimized gene transfection efficacy of L3 was nearly 5.5 times more efficient than that of the popular commercially available gene delivery agent Lipofectamine 2000™ in human lung carcinoma cells A549. In addition, since L1 and L3 had nearly no gene transfection performance in normal cells HEK293, these cationic lipids showed tumor cell-targeting property to a certain extent. No significant cytotoxicity was found for the lipoplexes formed by L1–L3, and their cytotoxicities were similar to or slightly lower than the lipoplexes prepared from Lipofectamine 2000™.ConclusionNovel cyclen-based cationic lipids for effective in vitro gene transfection were founded, and these studies here may extend the application areas of macrocyclic polyamines, especially for cyclen.

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“…As a typical compound in the macrocyclic polyamine family, 1, 4, 7, 10-tetraazacyclododecane (cyclen) has centralized amine density and non-folded conformations comparing to linear polyamines, and the relatively large pK a of the protonated amines may ensure its DNA-binding ability. Our previous studies focused on the synthesis of cyclen derivatives, their interactions with plasmid DNA, and gene delivery abilities (16)(17)(18)(19). It was revealed that many cyclen derivatives have great potential to be gene delivery vector.…”

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confidence: 99%

Cationic Lipids Containing Cyclen and Ammonium Moieties as Gene Delivery Vectors

Huang¹,

Ren²,

et al. 2012

Chem Biol Drug Des

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These authors contributed equally to this work.In this study, two novel cationic lipids containing protonated cyclen and quaternary ammonium moieties were designed and synthesized as non-viral gene delivery vectors. The structures of the two lipids differ in their hydrophobic region (cholesterol or diosgenin). Cationic liposomes were easily prepared from the lipids individually or from the mixtures of each cationic lipid and dioleoylphosphatidylethanolamine. Several studies including DLS, gel retardation assay, and ethidium bromide intercalation assay suggest that these amphiphilic molecules are able to bind and compact DNA into nanometer particles which can be used as non-viral gene delivery agents. Our results from in vitro transfection show that in association with dioleoylphosphatidylethanolamine, two cationic lipids can induce effective gene transfection in human embryonic kidney 293 cells, although the gene transfection efficiencies of two cationic lipids were found to be lower than that of lipofectamine 2000 TM . Besides, different cytotoxicity was found for two lipoplexes. This study demonstrates that the title cationic lipids have large potential to be efficient non-viral gene vectors.

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Diol glycidyl ether-bridged cyclens: preparation and their applications in gene delivery

Cited by 19 publications

References 36 publications

A Systematic Structure–Activity Study of a New Type of Small Peptidic Transfection Vector Reveals the Importance of a Special Oxo‐Anion‐Binding Motif for Gene Delivery

A Systematic Structure–Activity Study of a New Type of Small Peptidic Transfection Vector Reveals the Importance of a Special Oxo‐Anion‐Binding Motif for Gene Delivery

Cyclen-Based Cationic Lipids for Highly Efficient Gene Delivery towards Tumor Cells

Cationic Lipids Containing Cyclen and Ammonium Moieties as Gene Delivery Vectors

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