Assembly of amphiphilic nucleic acid-polymer conjugates into complex superaggregates: Preparation, properties, and in vitro performance

Bakardzhiev, Pavel; Toncheva-Moncheva, Natalia; Mladenova, Kirilka; Petrova, Svetla; Videv, Pavel; Moskova-Doumanova, Veselina; Topouzova-Hristova, Tanya; Doumanov, Jordan; Rangelov, Stanislav

doi:10.1016/j.eurpolymj.2020.109692

Cited by 11 publications

(16 citation statements)

References 67 publications

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“…To successfully shuttle nucleic acids, loaded drugs, and/or diagnostic agents into cells, SNAs can be properly designed in terms of architecture, functionality, molar mass, size, hydrophilic/lipophilic balance, etc., [ 16 , 17 , 18 ]. For instance, the selection of the right nanoparticle core plays a key role and directly determines the shape, size, and biological profiles of the core–shell assemblies [ 19 , 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Original Synthesis of a Nucleolipid for Preparation of Vesicular Spherical Nucleic Acids

et al. 2022

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Spherical nucleic acids (SNAs)—nanostructures, consisting of a nanoparticle core densely functionalized with a shell of short oligonucleotide strands—are a rapidly emerging class of nanoparticle-based therapeutics with unique properties and specific applications as drug and nucleic acid delivery and gene regulation materials. In this contribution, we report on the preparation of hollow SNA nanoconstructs by co-assembly of an originally synthesized nucleolipid—a hybrid biomacromolecule, composed of a lipidic residue, covalently linked to a DNA oligonucleotide strand—with other lipids. The nucleolipid was synthesized via a click chemistry approach employing initiator-free, UV light-induced thiol-ene coupling of appropriately functionalized intermediates, performed in mild conditions using a custom-made UV light-emitting device. The SNA nanoconstructs were of a vesicular structure consisting of a self-closed bilayer membrane in which the nucleolipid was intercalated via its lipid–mimetic residue. They were in the lower nanometer size range, moderately negatively charged, and were found to carry thousands of oligonucleotide strands per particle, corresponding to a grafting density comparable to that of other SNA structures. The surface density of the strands on the bilayer implied that they adopted an unextended conformation. We demonstrated that preformed vesicular structures could be successfully loaded with either hydrophilic or hydrophobic dyes.

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Section: Introductionmentioning

confidence: 99%

Original Synthesis of a Nucleolipid for Preparation of Vesicular Spherical Nucleic Acids

et al. 2022

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“…In that regard, a novel generation of oligonucleotide therapeutics has emerged which aims to conjugate oligonucleotides to ligands with the goal of enhancing the pharmacokinetic properties of the underlying drug (Juliano, Ming, & Nakagawa, 2012). Oligonucleotides conjugated to peptides (Patutina et al., 2018), polymers (Bakardzhiev et al., 2020), lipids (Wang, Allen, Prakash, Liang, & Crooke, 2019), and antibodies (Arnold et al., 2018)—among copious other ligands—have been reported, and their clinical success has been exemplified with the approval of Givosiran (Givlaari ™ ), which contains a covalently bonded, trivalent N ‐acetylgalactosamine (GalNAc) ligand for targeted delivery (Scott, 2020). Several methods for the preparation of oligonucleotide conjugates have been reported which to date rely on key chemical reactions such as Michael additions, amidations with amino‐modified oligonucleotides, copper‐catalyzed azide‐alkyne cycloadditions (CuAACs), and thiol‐disulfide exchanges (Singh, Murat, & Defrancq, 2010).…”

Section: Introductionmentioning

confidence: 99%

Preparation of a Convertible Spacer Containing a Disulfide Group for Versatile Functionalization of Oligonucleotides

Pontarelli

Liu

et al. 2023

Current Protocols

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The protocols described in this article provide details regarding the synthesis and characterization of a disulfide containing linker phosphoramidite for terminal functionalization of synthetic oligonucleotides. The linker is first synthesized from 6-mercaptohexanol in two steps and is incorporated at the 5 end of short DNA oligonucleotides using automated solid-phase synthesis. The linker contains a terminal tosylate group which is post-synthetically displaced by altering the deprotection conditions to yield a variety of functional handles (N 3 , NH 2 , OMe, SH) or alternatively, the tosylate can be displaced directly with primary amines such as tert-butylamine. The linker system is also compatible with RNA oligonucleotides enabling the introduction of various functional handles (N 3 , NH 2 ). The protocol outlined in this procedure provides access to a versatile linker for the terminal functionalization of oligonucleotides containing a disulfide bond which may serve useful in the synthesis of reduction-responsive oligonucleotide conjugates. As a proof of concept, in this protocol the linker is used to modify a dT 10 oligonucleotide and then conjugated by copper(I)-mediated azide-alkyne cycloaddition (CuAAC) to an alkyne-modified poly(ethylene glycol) which shows concentration dependent release of the oligonucleotide upon treatment with 1,4-dithiothreitol, a reducing agent.

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“…[8][9][10] In the recent years, a new class of nucleic acid delivery and gene regulation platforms, known as spherical nucleic acids (SNAs), has been developed. [11][12][13][14] SNAs are composed of highly oriented and densely grafted short oligonucleotide strands on the surface of a nanoparticle that can be inorganic (Au, 11 Ag, 15 silica 16 nanoparticles) or organic (protein, 17 polymer, [18][19][20][21][22][23] small molecules and drugs, [24][25][26] micelles, 27 mesoglobules 28 ). The oligonucleotide strands form a shell around the nanoparticles, which has been shown to provide colloidal stability under physiological conditions via electrostatic repulsion.…”

Section: Introductionmentioning

confidence: 99%

Hollow spherical nucleic acid structures based on polymer-coated phospholipid vesicles

et al. 2022

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Assembly of amphiphilic nucleic acid-polymer conjugates into complex superaggregates: Preparation, properties, and in vitro performance

Cited by 11 publications

References 67 publications

Original Synthesis of a Nucleolipid for Preparation of Vesicular Spherical Nucleic Acids

Original Synthesis of a Nucleolipid for Preparation of Vesicular Spherical Nucleic Acids

Preparation of a Convertible Spacer Containing a Disulfide Group for Versatile Functionalization of Oligonucleotides

Hollow spherical nucleic acid structures based on polymer-coated phospholipid vesicles

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