Multilayered thin films from poly(amido amine)s and DNA

Hujaya, Sry D.; Engbersen, Johannes F.J.

doi:10.1016/j.actbio.2015.04.022

Cited by 8 publications

(11 citation statements)

References 53 publications

(64 reference statements)

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“…The iterative repetition of deposition/washing steps can create multilayered architectures of controllable film thickness, composition, and hydrolytic stability. LbL assembly is well-suited for the encapsulation, protection, and release of therapeutic nucleic acids such as pDNA, siRNA, and others since the negative charge on nucleic acid backbones facilitates complexation with cationic polymers such as PLL, ,− chitosan, − and PEI. − In the context of gene delivery, LbL coatings are typically synthesized in the following formats: (1) the traditional approach to LbL assembly employs planar substrates, onto which polyelectrolytes are sequentially immobilized, creating nanometer-thick multilayer films (Figure A). ,− Further, nucleic acid cargoes can be impregnated within these films in the form of naked DNA or RNA, polyplexes, lipoplexes, , or simply as adenoviral capsids. (2) LbL coatings can be applied to nanoparticle , or microparticle , “cores” of desired shapes and sizes, such that the particle surface can be successively modified with polyelectrolytes, thereby transforming its interactions with cellular targets (Figure B) .…”

Section: Alternative Biomaterials Platforms For Transfectionmentioning

confidence: 99%

Polymeric Delivery of Therapeutic Nucleic Acids

et al. 2021

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The advent of genome editing has transformed the therapeutic landscape for several debilitating diseases, and the clinical outlook for gene therapeutics has never been more promising. The therapeutic potential of nucleic acids has been limited by a reliance on engineered viral vectors for delivery. Chemically defined polymers can remediate technological, regulatory, and clinical challenges associated with viral modes of gene delivery. Because of their scalability, versatility, and exquisite tunability, polymers are ideal biomaterial platforms for delivering nucleic acid payloads efficiently while minimizing immune response and cellular toxicity. While polymeric gene delivery has progressed significantly in the past four decades, clinical translation of polymeric vehicles faces several formidable challenges. The aim of our Account is to illustrate diverse concepts in designing polymeric vectors towards meeting therapeutic goals of in vivo and ex vivo gene therapy. Here, we highlight several classes of polymers employed in gene delivery and summarize the recent work on understanding the contributions of chemical and architectural design parameters. We touch upon characterization methods used to visualize and understand events transpiring at the interfaces between polymer, nucleic acids, and the physiological environment. We conclude that interdisciplinary approaches and methodologies motivated by fundamental questions are key to designing high-performing polymeric vehicles for gene therapy.

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Section: Alternative Biomaterials Platforms For Transfectionmentioning

confidence: 99%

Polymeric Delivery of Therapeutic Nucleic Acids

et al. 2021

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“…In vitro condensation of DNA has been studied both theoretically [18,19] and experimentally [20] and still remains of topical interest, especially when surface-mediated delivery of DNA is foreseen [21][22][23]. To condense DNA in aqueous media, at least the presence of a salt is required to neutralize DNA charges and decrease DNA-DNA poly-anion repulsion.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…As ESD studies do not generally require further gel electrophoresis analysis, the protocol exposed herein may be extremely useful in such research areas in relation with fundamental radiobiology. Such layers, containing Tris or not, will also most probably find applications in areas where plasmid DNA deposits are used for the controlled release of therapeutic macromolecules [44,45]. Lastly, when present in the solution, the Tris buffer undoubtedly ensures conservation of a maximum percentage of supercoiled topology of the…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Auto-assembly of nanometer thick, water soluble layers of plasmid DNA complexed with diamines and basic amino acids on graphite: Greatest DNA protection is obtained with arginine

Khalil

Boulanouar

Heintz

et al. 2017

Materials Science and Engineering: C

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“…[36][37][38] The multilayered nature of these coatings allows exquisite control over loading, release kinetics, and porosity (from smooth to highly porous surfaces); while their nanometer-thickness scale preserves the architecture of substrates with complex geometries. [39,40] This has been used to deliver a variety of cargoes that include proteins, [39][40][41][42] drugs, [43,44] nucleic acids, [45][46][47][48] and particle systems. [49,50] Therefore, we have combined self-assembled polyplex-polysaccharide nanofilms with high-aspect ratio nanostructures to synergistically enhance nucleic acid delivery and transfection efficiency.…”

Section: Introductionmentioning

confidence: 99%

Polysaccharide‐Polyplex Nanofilm Coatings Enhance Nanoneedle‐Based Gene Delivery and Transfection Efficiency

Hachim

Zhao

Bhankharia

et al. 2022

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Non‐viral vectors represent versatile and immunologically safer alternatives for nucleic acid delivery. Nanoneedles and high‐aspect ratio nanostructures are unconventional but interesting delivery systems, in which delivery is mediated by surface interactions. Herein, nanoneedles are synergistically combined with polysaccharide‐polyplex nanofilms and enhanced transfection efficiency is observed, compared to polyplexes in suspension. Different polyplex‐polyelectrolyte nanofilm combinations are assessed and it is found that transfection efficiency is enhanced when using polysaccharide‐based polyanions, rather than being only specific for hyaluronic acid, as suggested in earlier studies. Moreover, results show that enhanced transfection is not mediated by interactions with the CD44 receptor, previously hypothesized as a major mechanism mediating enhancement via hyaluronate. In cardiac tissue, nanoneedles are shown to increase the transfection efficiency of nanofilms compared to flat substrates; while in vitro, high transfection efficiencies are observed in nanostructures where cells present large interfacing areas with the substrate. The results of this study demonstrate that surface‐mediated transfection using this system is efficient and safe, requiring amounts of nucleic acid with an order of magnitude lower than standard culture transfection. These findings expand the spectrum of possible polyelectrolyte combinations that can be used for the development of suitable non‐viral vectors for exploration in further clinical trials.

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Multilayered thin films from poly(amido amine)s and DNA

Cited by 8 publications

References 53 publications

Polymeric Delivery of Therapeutic Nucleic Acids

Polymeric Delivery of Therapeutic Nucleic Acids

Auto-assembly of nanometer thick, water soluble layers of plasmid DNA complexed with diamines and basic amino acids on graphite: Greatest DNA protection is obtained with arginine

Polysaccharide‐Polyplex Nanofilm Coatings Enhance Nanoneedle‐Based Gene Delivery and Transfection Efficiency

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