TACN-containing cationic lipids with ester bond: preparation and application in gene delivery.
ABSTRACT A series of novel cationic lipids based on 1,4,7-triazacyclononane (TACN) with different hydrophobic chains were synthesized via the formation of a biodegradable ester bond. These lipids were found to have good buffering capacity at the pH range of 5.0-6.5, which is similar to that of the acidic endosomal compartments. The liposomes formed from these lipids and DOPE could condense DNA into nanoparticles with proper sizes. In vitro experiments showed moderate to good gene transfection efficiency of the formed lipoplexes. The structure-activity relationships of this type of lipids were discussed.
- SourceAvailable from: Rafique Ul Islam[Show abstract] [Hide abstract]
ABSTRACT: Two nitrogen-pivoted aza-crown ethers (aza-CEs) linked to the cholesteryl-fused ring system N-(cholesteryloxycarbonyl)aza-15-crown-5 and N-(cholesteryloxycarbonyl)aza-18-crown-6 have been incorporated into cationic liposomes containing the cytofectin 3β[N-(N′,N′-dimethylaminopropane) carbamoyl] cholesterol (Chol-T) and the neutral co-lipid dioleoylphosphatidylethanolamine. These novel liposomes form stable complexes with plasmid DNA and afford it good protection from serum nuclease digestion. Ethidium displacement studies suggest that the DNA is more loosely packed in aza-CE containing lipoplexes, a finding which is supported by band shift assays that reveal N/P end point ratios of 2:1, 3:1 and 3.5:1 for Chol-T control liposomes, aza-15-crown-5 and aza-18-crown-6 containing liposomes, respectively. The transfection activities of crown ether-containing lipoplex formulations in the human embryonic kidney cell line HEK293 are twofold greater than those achieved by Chol-T lipoplexes not containing the aza-CEs. This observation may be attributable to the more loosely packed DNA, which facilitates disassembly, and to endosomal perturbations caused by macrocycle entrapped cations.Medicinal Chemistry Research 06/2013; 22(6):2561-2569. · 1.61 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The transfection of DNA in gene therapy largely depends on the possibility of obtaining its condensation. The details of nanoparticles formation are essential for functioning, as mediated by the diverse elements containing molecular structure, ionic strength in mediums, and condensing motivator. Here, we reported two kinds of DNA condensing agents based on simple cyclic/rigid polyamine molecules, and evaluated their structural effect on nanoparticles formation. Reversible condensation-dissociation process was achieved by ion-switching, attributing to a possible condensing mechanism - competitive building of external hydrogen bonds. Using poly[(dA-dT)2] and poly[(dG-dC)2] as substrates respectively, circular dichroism (CD) signals clearly presented dissimilar interactions between polyamines and both rich sequences, implying potential preference for G-C sequence. The presence of divalent ion Zn2+ as an efficient motivator accelerated the achievement of DNA condensation, and an accessible schematic model was depicted to explain the promotion in detail. In addition, by comparison with the behaviors of linear polyamines, differences between condensation and aggregation were explicitly elucidated in aspects of morphology and surface charges, as well as induced condition. The present work may have the potential to reveal the precise mechanism of DNA nanoparticles formation, in particular, be applied to gene delivery as an efficient non-viral vector.The Journal of Physical Chemistry B 06/2013; · 3.61 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Three small organic molecules containing different numbers of cyclen and imidazolium units were synthesized. Their interactions with plasmid DNA and their potential for gene delivery vectors were investigated. Agarose gel retardation and ethidium bromide exclusion assays revealed that these molecules can effectively condense DNA, and compounds with higher molecular weights are needed to lower w/w ratio for full condensation. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) indicated that these compounds may form nanosized spherical particles with DNA. Furthermore, the complex formed from 10, i.e., 10/DNA, can partially release DNA from compact state at a relatively higher concentration of NaCl (200 mM). In the presence of the lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), 10 could transfer plasmid DNA into BEL-7402 cells. In addition, these compounds exhibited much lower cytotoxicity than PEI 25 kDa.Chemistry & Biodiversity 02/2014; 11(2):233-44. · 1.81 Impact Factor