Amphiphilic Dendrimers: Novel Self‐Assembling Vectors for Efficient Gene Delivery

Joester, Derk; Losson, Myriam; Pugin, Raphaël; Heinzelmann, H.; Walter, Elke; Merkle, Hans P.; Diederich, François

doi:10.1002/anie.200250284

Cited by 172 publications

(25 citation statements)

References 31 publications

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“…This leads us to conclude that upon protonation of the histidine moi eties the nanorodlike supramolecular copolymers disassemble and the multivalent electrostatic points of interaction between the polycationic peptide copolymer and the polyanionic siRNA are lost. [25] Note, that we cannot exclude that the released cati onic comonomer 2 still binds to the siRNA. In summary, the microscopic results corroborate the spectroscopic findings.…”

Section: Resultsmentioning

confidence: 97%

Tuning the pH‐Switch of Supramolecular Polymer Carriers for siRNA to Physiologically Relevant pH

Ahlers

Frisch

Holm

et al. 2017

Macromolecular Bioscience

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Aqueous supramolecular polymers [4] have recently entered the field of biomed ical applications [5] and several systems have been disclosed for regenerative medi cine or drug delivery, using host-guest pairs, [6] peptide amphiphiles, [7] ureido pyrimidineone, [8] and benzenetricarbox amide (BTA) [9] scaffolds. We here focus on the use of 1D supramolecular polymers, with a nanorodlike morphology, based on new dendritic oligo(histidine-alt-phenyla lanine) peptide synthons. These combine high robustness and fidelity in the self assembly with stimuliresponsive proper ties toward pHvalues of the surrounding medium. We have previously reported C 3 symmetrical nonaphenylalanine supra molecular building monomers equipped with dendritic tetraethylene glycol chains, with binding affinities of up to 7 × 10 7 m −1 in water. [10] In order to introduce pHswitchable properties into the supramolecular polymeriza tion, we changed the peripheral dendritic tetraethylene glycol chains for dendritic carboxylic acids in the amphiphilic mono mers that are highly charged and thus molecularly dissolved at neutral pH and selfassemble into anisotropic supramolecular polymers by acidifying the aqueous medium. [11] These sys tems were not applicable when aiming for a pHtriggered dis assembly of supramolecular constructs upon lowering the pH. To this end we have disclosed an ampholytic supramolecular copolymer design, whereby the multicomponent coassembly of anionic oligo(glutamic acid-alt-phenylalanine) and cationic oligo(lysine-alt-phenylalanine) peptide synthons leads to alter nating copolymer formation. [12] The pHstability window of these copolymers could be tuned by a supramolecular engi neering approach, using mismatched comonomer pairs which shifts the pHtriggered disassembly of the copolymers from pH 4.2 to 5.8. [13] In this case however the pHtriggered glutamic acid monomer that is released upon disassembly of the copol ymers leads to the formation of homopolymers, in a process that is driven by charge regulation. [2c,12b,13] Thus, we here aim to develop a facile pHresponsive supramolecular polymeriza tion using an oligo(histidine-alt-phenylalanine) peptide syn thon, that operates in a physiologically relevant pH window, and where the functional and structural dendritic comonomers can be mixed at will, without significantly shifting the pHtriggered disassembly. The hydrophobic-hydrophilic shift upon protona tion of histidine containing amphiphiles under slightly acidic pH-triggered ReleaseThe preparation of histidine enriched dendritic peptide amphiphiles and their self-assembly into multicomponent pH-switchable supramolecular polymers is reported. Alternating histidine and phenylalanine peptide synthons allow the assembly/disassembly to be adjusted in a physiologically relevant range of pH 5.3-6.0. Coassembly of monomers equipped with dendritic tetraethylene glycol chains with monomers bearing peripheral primary amine groups leads to nanorods with a tunable cationic surface charge density. These surface functional supramolecula...

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Section: Resultsmentioning

confidence: 97%

Tuning the pH‐Switch of Supramolecular Polymer Carriers for siRNA to Physiologically Relevant pH

Ahlers

Frisch

Holm

et al. 2017

Macromolecular Bioscience

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“…Thus, careful manipulation of the amphiphilic counterpart is necessary to achieve a more favorable HLB to form stable gene vehicles with appropriate shape and morphology (e.g., spheroid or vesicle-like), thus facilitating DNA complexation, cellular uptake, and gene transfection. [27][28][29][30] In the current study, we demonstrate a facile synthesis of amphiphilic PAMAM dendron-bearing fullerene derivative, by using an efficient Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC). 31 We found that the click cluster, interconnecting the diazido-functionalized fullerene and PAMAM dendrons bearing a propargyl focal point via a 1,4-triazole linkage, is highly water-soluble and is readily prepared in high yield without the need for chromatographic purification.…”

Section: Introductionmentioning

confidence: 99%

Self‐aggregation of amphiphilic [60]fullerenyl focal point functionalized PAMAM dendrons into pseudodendrimers: DNA binding involving dendriplex formation

Hung

Chang

Liu

et al. 2014

J Biomedical Materials Res

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In this research, we successfully performed a "click" synthesis of amphiphilic poly(amido amine) dendron-bearing fullerenyl conjugate (C60 G1 ) using a copper(I)-catalyzed azide-alkyne cycloaddition reaction. The strong hydrophobicity of the C60 moiety induces self-assembly of C60 G1 into core-shell-like "pseudodendrimers" with a uniform size distribution and positively charged peripherals. The pseudodendrimers were well-characterized by atomic force microscopy (AFM), transmission electron microscopy, and dynamic light scattering. On the basis of electrostatic interactions, the polycationic C60 G1 assembly can serve as a nonviral gene vector. An ethidium bromide displacement assay and agarose gel electrophoresis both indicated that C60 G1 assembly forms stable complexes with the cyclic reporter gene (pEGFP-C1) at low nitrogen-to-phosphorous (N/P) ratios. AFM analysis revealed a dynamic complex-formation process, and confirmed the synthesis of C60 G1 /pEGFP-C1 hybrids with a particle dimensions less than 200 nm. Fluorescence microscopy and flow cytometry revealed that 51% of HeLa and 43% of MCF-7 cells are positive to the YOYO-1-labeled hybrids at an N/P ratio of 2, being comparable to TurboFect-mediated delivery.

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“…The consumption of linear low density polyethylene (LLDPE) in Russia alone has been predicted to increase from 90,000 metric tons in 2007 to 1,00,000 metric tons in 2008 and the percentage increase in LLDPE use in China is in double-digit figures. The significant consumption is explained by the fact that polymers have found a wide area of application in virtually all areas of life, from simple packaging and building materials to more sophisticated uses in engineering applications requiring high-performance materials as well as in medicine (both as biomaterials [1][2][3] and in drug- [4][5][6][7][8][9][10][11] and gene delivery [12][13][14][15][16][17][18][19]), home and personal care applications [20,21] and as plastic and printed electronics [22][23][24][25][26]. The reason for the success of polymers as materials can be found in the combination of a number of reasons: (1) commodity polymers are cheap to manufacture (the average cost of crude-derived commodity polymers is approximately 1 d/kg) [27], (2) polymers are largely non-toxic, (3) polymers are easy to process, (4) polymers are easy to adapt through post-processing and additives and (5) polymers are on the whole stable and relatively tough.…”

Section: Introductionmentioning

confidence: 99%

Polymer Informatics

Adams

2010

Polymer Libraries

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Polymers are arguably the most important set of materials in common use. The increasing adoption of both combinatorial as well as high-throughput approaches, coupled with an increasing amount of interdisciplinarity, has wrought tremendous change in the field of polymer science. Yet the informatics tools required to support and further enhance these changes are almost completely absent. In the first part of the chapter, a critical analysis of the challenges facing modern polymer informatics is provided. It is argued, that most of the problems facing the field today are rooted in the current scholarly communication process and the way in which chemists and polymer scientists handle and publish data. Furthermore, the chapter reviews existing modes of representing and communicating polymer information and discusses the impact, which the emergence of semantic technologies will have on the way in which scientific and polymer data is published and transmitted. In the second part, a review of the use of informatics tools for the prediction of polymer properties and in silico design of polymers is offered.

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Amphiphilic Dendrimers: Novel Self‐Assembling Vectors for Efficient Gene Delivery

Cited by 172 publications

References 31 publications

Tuning the pH‐Switch of Supramolecular Polymer Carriers for siRNA to Physiologically Relevant pH

Tuning the pH‐Switch of Supramolecular Polymer Carriers for siRNA to Physiologically Relevant pH

Self‐aggregation of amphiphilic [60]fullerenyl focal point functionalized PAMAM dendrons into pseudodendrimers: DNA binding involving dendriplex formation

Polymer Informatics

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