Serum tolerance and endosomal escape capacity of histidine-modified pDNA-loaded complexes based on polyamidoamine dendrimer derivatives

Wen, Yuting; Guo, Zhenhuan; Du, Zhuo; Fang, Rong; Wang, Hongmei; Zeng, Xiaofeng; Wang, Chi; Feng, Min; Pan, Shaowei

doi:10.1016/j.biomaterials.2012.07.032

Cited by 90 publications

(65 citation statements)

References 25 publications

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“…The addition of bafilomycin A1, which inhibits the acidification in endosome and lysosome, can efficiently block the transfection of EGFP gene by G5-F7 68 , whereas the supplement of sucrose, a lysosomotropic agent that accelerates the escape of polyplexes from acidic vesicles, cannot further improve the transfection efficacy of G5-F7 68 ( Supplementary Fig. 15) 44,45 . The efficient cellular uptake and endosomal escape of G5-F7 68 /DNA polyplexes are further confirmed by confocal microscopy.…”

Section: Resultsmentioning

confidence: 99%

A fluorinated dendrimer achieves excellent gene transfection efficacy at extremely low nitrogen to phosphorus ratios

et al. 2014

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Polymers have shown great promise in the design of high efficient and low cytotoxic gene vectors. Here we synthesize fluorinated dendrimers for use as gene vectors. Fluorinated dendrimers achieve excellent gene transfection efficacy in several cell lines (higher than 90% in HEK293 and HeLa cells) at extremely low N/P ratios. These polymers show superior efficacy and biocompatibility compared with several commercial transfection reagents such as Lipofectamine 2000 and SuperFect. Fluorination enhances the cellular uptake of the dendrimer/DNA polyplexes and facilitates their endosomal escape. In addition, the fluorinated dendrimer shows excellent serum resistance and exhibits high gene transfection efficacy even in medium containing 50% FBS. The results suggest that fluorinated dendrimers are a new class of highly efficient gene vectors and fluorination is a promising strategy to design gene vectors without involving sophisticated syntheses.

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Section: Resultsmentioning

confidence: 99%

A fluorinated dendrimer achieves excellent gene transfection efficacy at extremely low nitrogen to phosphorus ratios

et al. 2014

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“…A different approach to reduce cytotoxicity in polycationic vectors was to introduce hydrolyzable linkages, as the ester groups, as applied both to PAMAM 30 itself and to non dendrimeric vectors such as poly(β-amino esters). [31][32][33] Moreover, dendrimers containing amino acid residues 26,[34][35][36] have aroused great interest since the diversity of amino acid moiety can meet the recognized requirement for modulating the buffer capacity of the vector and facilitate its escape from endosomal acidic compartments through membrane disruption of endosomes. 10 On this ground, with the aim of preparing hydrolyzable dendrimer structures which were, at the same time, adequately protonated but also well tolerated by the cells and which could harmonize transfection capacity with a low level of toxicity, we report in this work versatile chemical protocols for the synthesis of a library of 15 dendrimers of fourth, fifth and sixth generation derived from 2,2-bis(hydroxymethyl)propanoic acid (bis-HMPA), a monomer of the AB 2 type used to prepare a variety of dendritic architectures.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and NMR characterization of dendrimers based on 2, 2-bis-(hydroxymethyl)-propanoic acid (bis-HMPA) containing peripheral amino acid residues for gene transfection

Alfei¹,

Castellaro²,

Taptue³

2017

Org. Commun.

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Dendrimers, the emerging man made, highly branched, star-shaped macromolecules with nanometerscale dimensions are well known for their well defined and high controlled architecture, their versatility and high functionality and are of eminent interest in nanomedical applications such as drug delivery, gene transfection, and imaging. In this paper, versatile protocols for the synthesis of polyester-based, hydrolysable, polycationic dendrimers have been setup. A fourth generation dendrimer equipped with 48 peripheral hydroxyl groups was prepared from 2,2-bis(hydroxymethyl)propanoic acid and was used for grafting BOC-amino acids or as "hypercores" on which dendrons functionalized with BOC-amino acids were attached. A library of 15 polycationic homo-and hetero-dendrimers in the form of hydrochloride was obtained. Their structures and composition were confirmed by NMR analysis and by experimental molecular weight computed by volumetric titration. Their buffer capacity and results obtained from cytotoxicity assays and tests of binding with both pDNA and siRNA were very satisfactory. Keywords:Polyester-based polycationic dendrimers; 2, 2-bis(hydroxymethyl)propanoic acid; amino acids; pDNA and siRNA binding; buffer capacity.

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“…It is also known that the physical stability of gene delivery systems in serum is a very important factor affecting their use in vivo. 32 High transfection efficiency was obtained under serum conditions (Figure 4), suggesting that CA-CSO-SA may be useful for transfection in vivo.…”

Section: Discussionmentioning

confidence: 97%

Efficient gene delivery system mediated by cis-aconitate-modified chitosan-g-stearic acid micelles

Yao¹,

Du²,

Yuan³

et al. 2014

IJN

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Cis-aconitate-modified chitosan-g-stearic acid (CA-CSO-SA) micelles were synthesized in this study to improve the gene transfection efficiency of chitosan-g-stearic acid (CSO-SA). The CA-CSO-SA micelles had a similar size, critical micelle concentration, and morphology, but their zeta potential and cytotoxicity were reduced compared with CSO-SA micelles. After modification with cis-aconitate, the CA-CSO-SA micelles could also compact plasmid DNA (pDNA) to form nanocomplexes. However, the DNA binding ability of CA-CSO-SA was slightly reduced compared with that of CSO-SA. The transfection efficiency mediated by CA-CSO-SA/pDNA against HEK-293 cells reached up to 37%, and was much higher than that of CSO-SA/pDNA (16%). Although the cis-aconitate modification reduced cellular uptake kinetics in the initial stages, the total amount of cellular uptake tended to be the same after 24 hours of incubation. An endocytosis inhibition experiment showed that the internalization mechanism of CA-CSO-SA/pDNA in HEK-293 cells was mainly via clathrin-mediated endocytosis, as well as caveolae-mediated endocytosis and macropinocytosis. Observation of intracellular trafficking indicated that the CSO-SA/pDNA complexes were trapped in endolysosomes, but CA-CSO-SA/pDNA was more widely distributed in the cytosol. This study suggests that modification with cis-aconitate improves the transfection efficiency of CSO-SA/pDNA.

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Serum tolerance and endosomal escape capacity of histidine-modified pDNA-loaded complexes based on polyamidoamine dendrimer derivatives

Cited by 90 publications

References 25 publications

A fluorinated dendrimer achieves excellent gene transfection efficacy at extremely low nitrogen to phosphorus ratios

A fluorinated dendrimer achieves excellent gene transfection efficacy at extremely low nitrogen to phosphorus ratios

Synthesis and NMR characterization of dendrimers based on 2, 2-bis-(hydroxymethyl)-propanoic acid (bis-HMPA) containing peripheral amino acid residues for gene transfection

Efficient gene delivery system mediated by cis-aconitate-modified chitosan-g-stearic acid micelles

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