Tools of gene transfer applied to the intracellular delivery of non-nucleic acid polyanionic drugs

Kryger, Mille B. L.; Pedersen, Søren Lykke; Wohl, Benjamin M.; Zelikin, Alexander N.

doi:10.1039/c5cc08011h

Cited by 5 publications

(4 citation statements)

References 20 publications

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“…Even though these compounds have still a long way to go for reaching the clinic, they constitute a novel class of artificial vectors promoting cell penetration and nucleic acids complexation for drug and gene delivery. It is worth pointing out that some of these polycationic systems may also find other biological applications as vectors of non-nucleic acid polyanionic drugs, 138 synthetic anti-microbials, 139 anti-viral, 51 or anti-tumor agents. 62 Their strong adhesion to polyanionic surfaces may also be of interest in material science.…”

Section: Discussionmentioning

confidence: 99%

Bioactive clusters promoting cell penetration and nucleic acid complexation for drug and gene delivery applications: from designed to self-assembled and responsive systems

et al. 2016

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Bioactive low-molecular-weight compounds are actively pursued, as an alternative to macromolecules, for biomedical applications such as drug and gene delivery. However, achieving effective biomolecular surface recognition with small molecules is a considerable challenge. We review herein recent progresses that have been made in the identification of bioactive cationic clusters that promote cell penetration and nucleic acid complexation and vectorisation. We further emphasize the emerging use of self-assembly processes, based on supramolecular interactions and/or dynamic covalent chemistry, for generating bioactive cationic clusters. Interestingly, the introduction of molecular and/or supramolecular dynamics endows reversibility to the multivalent recognition processes, thereby paving the way toward the development of "smart" adaptive and responsive devices that emulate the behaviour of natural systems for the dynamic control of bioactivity.

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Section: Discussionmentioning

confidence: 99%

Bioactive clusters promoting cell penetration and nucleic acid complexation for drug and gene delivery applications: from designed to self-assembled and responsive systems

et al. 2016

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“…50% reduction in the levels of NO at sub-toxic concentrations of the drug [37]. It is worthy of note that polyanions are typically deemed to have restricted cell entry [66]. However, confocal laser scanning microscopy evaluation of the polymer uptake by macrophages revealed pronounced polymer-associated fluorescence inside the cells (Fig.…”

Section: Anti-inflammatory Propertiesmentioning

confidence: 94%

Macromolecular prodrugs of ribavirin: Polymer backbone defines blood safety, drug release, and efficacy of anti-inflammatory effects

Zuwała

Riber

Løvschall

et al. 2018

Journal of Controlled Release

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Macromolecular (pro)drugs hold much promise as broad-spectrum antiviral agents as either microbicides or carriers for intracellular delivery of antiviral drugs. Intriguing opportunity exists in combining the two modes of antiviral activity in the same polymer structure such that the same polymer acts as a microbicide and also serves to deliver the conjugated drug (ribavirin) into the cells. We explore this opportunity in detail and focus on the polymer backbone as a decisive constituent of such formulations. Fourteen polyanions (polycarboxylates, polyphosphates and polyphosphonates, and polysulfonates) were analyzed for blood pro/anti coagulation effects, albumin binding and albumin aggregation, inhibitory activity on polymerases, cytotoxicity, and anti-inflammatory activity in stimulated macrophages. Ribavirin containing monomers were designed to accommodate the synthesis of macromolecular prodrugs with disulfide-exchange triggered drug release. Kinetics of drug release was fast in all cases however enhanced hydrophobicity of the polymer significantly slowed release of ribavirin. Results of this study present a comprehensive view on polyanions as backbone for macromolecular prodrugs of ribavirin as broad-spectrum antiviral agents.

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“…Polycations with positive charges have been described as possessing characteristics such as anti-peroxidation, anti-tumor, and anti-inflammation [27,28]. Polyanions with negative charges are broadly applied in drug delivery, chemical synthesis, and so on [29,30]. Chain structure, electrostatic force, reactive amine groups, active chemical bonds, and nucleophilicity underpin the essential differences between different polyelectrolytes.…”

Section: Biomaterials Employed In Lbl Cell Encapsulationmentioning

confidence: 99%

Layer-by-Layer Cell Encapsulation for Drug Delivery: The History, Technique Basis, and Applications

Lei

Feng

et al. 2022

Pharmaceutics

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The encapsulation of cells with various polyelectrolytes through layer-by-layer (LbL) has become a popular strategy in cellular function engineering. The technique sprang up in 1990s and obtained tremendous advances in multi-functionalized encapsulation of cells in recent years. This review comprehensively summarized the basis and applications in drug delivery by means of LbL cell encapsulation. To begin with, the concept and brief history of LbL and LbL cell encapsulation were introduced. Next, diverse types of materials, including naturally extracted and chemically synthesized, were exhibited, followed by a complicated basis of LbL assembly, such as interactions within multilayers, charge distribution, and films morphology. Furthermore, the review focused on the protective effects against adverse factors, and bioactive payloads incorporation could be realized via LbL cell encapsulation. Additionally, the payload delivery from cell encapsulation system could be adjusted by environment, redox, biological processes, and functional linkers to release payloads in controlled manners. In short, drug delivery via LbL cell encapsulation, which takes advantage of both cell grafts and drug activities, will be of great importance in basic research of cell science and biotherapy for various diseases.

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Tools of gene transfer applied to the intracellular delivery of non-nucleic acid polyanionic drugs

Cited by 5 publications

References 20 publications

Bioactive clusters promoting cell penetration and nucleic acid complexation for drug and gene delivery applications: from designed to self-assembled and responsive systems

Bioactive clusters promoting cell penetration and nucleic acid complexation for drug and gene delivery applications: from designed to self-assembled and responsive systems

Macromolecular prodrugs of ribavirin: Polymer backbone defines blood safety, drug release, and efficacy of anti-inflammatory effects

Layer-by-Layer Cell Encapsulation for Drug Delivery: The History, Technique Basis, and Applications

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