Evaluation of cationic dendrimer and lipid as transfection reagents of short RNAs for stem cell modification

Ziraksaz, Zarrintaj; Nomani, Alireza; Soleimani, Masoud; Bakhshandeh, Behnaz; Arefian, Ehsan; Haririan, Ismaeil; Tabbakhian, Majid

doi:10.1016/j.ijpharm.2013.03.035

Cited by 22 publications

(32 citation statements)

References 23 publications

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“…We chose the widely used dendrimer as a model to test the influence of the size and surface group as well as cytotoxicity and endocytosis on the hESC gene transfection. Our work is irrespective of those reports on dendrimer variable gene transfer efficacy in different cell types 18,20 and different from those observations of mere cytotoxicity but no influence on cellular differentiation of amino functionalized dendrimers for mesenchymal stem cells.…”

Section: ■ Discussioncontrasting

confidence: 99%

Improving the Gene Transfection in Human Embryonic Stem Cells: Balancing with Cytotoxicity and Pluripotent Maintenance

Luo

Lü

Pan

et al. 2016

ACS Appl. Mater. Interfaces

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Manipulation of genes in human embryonic stem cells (hESCs) is imperative for their highly potential applications; however, the transduction efficiency remains very low. Although existing evidence revealed the type, size, and zeta potential of vector affect gene transfection efficiency in cells, the systematic study in hESCs is scarce. In this study, using poly(amidoamine) (PAMAM) dendrimers ended with amine, hydroxyl, or carboxyl as model, we tested the influences of size and surface group as well as cytotoxicity and endocytosis on hESC gene transfection. We found that in culture medium of mTeSR the particle sizes of G5, G7, G4.5COOH, and G5OH were around 5 nm and G1 had a smaller size of 3.14 nm. G5 and G7 had a slight and significant positive zeta potential, respectively, whereas G1 was slightly negative, and G4.5COOH and G5OH were significantly negative. We demonstrated that only amine-terminated dendrimers accomplished gene transfection in hESCs, which is greater than that from Lipofectamine 2000 transfection. Ten micromolar G5 had the greatest efficiency and was better than 1000 μM G1. Only a low concentration (0.5 and 1 μM) of G7 realized gene delivery. Amine-ended dendrimers, especially with higher generations, were detrimental to the growth and pluripotent maintenance of hESCs. In contrast, similarly sized hydroxyl-and carboxyl-terminated dendrimers exerted much lower cytotoxicity, in which carboxyl-terminated dendrimer maintained pluripotency of hESCs. We also confirmed the endocytosis into and significant exocytosis from hESCs using FITC-labeled G5 dendrimer. These results suggested that careful considerations of size, concentration, and zeta potential, particularly the identity and position of groups, as well as minimized exocytosis in the design of a vector for hESC gene delivery are necessary, which helps to better design an effective vector in hESC gene transduction.

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Section: ■ Discussioncontrasting

confidence: 99%

Improving the Gene Transfection in Human Embryonic Stem Cells: Balancing with Cytotoxicity and Pluripotent Maintenance

Luo

Lü

Pan

et al. 2016

ACS Appl. Mater. Interfaces

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“…The dendriplexes were saturated at a charge ratio of 3 for CPD and 6-10 for PAMAM and CBD. Positive zeta potentials were also obtained for CBD interactions with anti-HIV oligonucleotides (Ionov et al, 2013b), as well as for PAMAM and CPD complexation with siRNA (Suzuki et al, 1997Ziraksaz et al, 2013. The positive charges on the surface of dendriplexes favor interactions with cell membranes and the internalization process.…”

Section: Discussionmentioning

confidence: 91%

Anticancer siRNA cocktails as a novel tool to treat cancer cells. Part (A). Mechanisms of interaction

Йонов

Łaźniewska

Dzmitruk

et al. 2015

International Journal of Pharmaceutics

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“…The transfection of mouse embryonic stem cells (mESCs) was analyzed using flow cytometry and quantitative real-time polymerase chain reaction (qPCR). The authors concluded that DOTAP at higher molar ratios and PAMAM at lower molar ratios had the ability to knockdown octamerbinding transcription factor (OCT4) transcription more effectively than the commercially available reagent Arrest-In TM [40].…”

Section: Figurementioning

confidence: 99%

PAMAM dendrimers as promising nanocarriers for RNAi therapeutics

et al. 2015

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Therapeutics based on RNA interference mechanisms are highly promising for the management of several diseases including multi-drug resistant cancers. However, effective delivery of siRNAs and oligonucleotides still remains challenging. In this regard, hyper-branched, PAMAM dendrimers having unique three-dimensional architecture and nanoscale size, with cationic surface charge can potentially serve as siRNA condensing agents as well as robust nano-vectors for targeted delivery. In addition, their surface functionality permits conjugation of drugs and genes or development of hybrid systems for combination therapy. Thus far, in vitro cellular testing of dendrimer-mediated siRNA delivery has revealed great potential, with reports on their in vivo effectiveness starting to appear. These favorable outcomes portend a promising future for dendrimer mediated RNAi therapeutics.

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Evaluation of cationic dendrimer and lipid as transfection reagents of short RNAs for stem cell modification

Cited by 22 publications

References 23 publications

Improving the Gene Transfection in Human Embryonic Stem Cells: Balancing with Cytotoxicity and Pluripotent Maintenance

Improving the Gene Transfection in Human Embryonic Stem Cells: Balancing with Cytotoxicity and Pluripotent Maintenance

Anticancer siRNA cocktails as a novel tool to treat cancer cells. Part (A). Mechanisms of interaction

PAMAM dendrimers as promising nanocarriers for RNAi therapeutics

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