Nucleic Acid-Nanoparticle Conjugates

Nucleic acid-nanoparticle conjugates are synthesized between appropriately functionalized oligonucleotides and nanoparticles with different properties and compositions. Drawing on our expertise in the field of bioconjugation, CD Bioparticles has developed strategies to provide our scientific and industrial clients with custom nucleic acid-nanoparticle complex synthesis and conjugation services.

Introduction to Nucleic Acid-Nanoparticle Conjugates

As we all know, nucleic acid has various forms, such as DNA, aptamer and siRNA, to express its biological activity. This provides the structural basis and functional features for designing complex biocomposites. Among them, the self-assembling nature of DNA strands is attributed to the formation of intermolecular hydrogen bonds between purine (adenine and guanine) and pyrimidine (thymine and cytosine) bases in nucleic acids. Therefore, conjugates with bases also exhibit interesting supramolecular self-assembly or self-sorting properties. Among them, the polymer and nucleic acid conjugation technology has been relatively mature, and its main method is often used at the end of the oligonucleotide sequence to produce a block copolymer containing nucleic acid.

Figure 1. Spherical nucleic acids nanoconjugates. (Mirkin CA, et al.; 2014)

Superior tissue properties are obtained when synthetic polymers are conjugated to oligonucleotides. Unlike previous approaches, this supramolecular organization is not based on random nucleobase recognition, but is driven by sequence-defined cooperative association of oligomers. In addition, since oligonucleotides have an optimized backbone structure of natural nucleic acids, complementary self-assembly of oligonucleotides can be achieved in water. For example, hydrophilic synthetic polymers and hydrophobic oligonucleotide segments can form amphiphilic blocks of block copolymers. nanoparticles) assemble with each other to form a superstructure of aqueous micelles. In addition, bioconjugates of polymers and oligonucleotides can be used to construct microbiological or biotechnological materials, such as DNA microarrays for diagnostic testing. Currently, oligonucleotides have been conjugated to a variety of synthetic polymers, including polypyrrole, polynorbornene, poly(maleic anhydride-acrylate) copolymer, poly(N-vinylpyrrolidone-co-N-propylene Acyloxysuccinimide) copolymer, poly(N-2,2-dimethoxyethyl-N-methacrylamide) and poly(N-acryloylmorpholine-co-N-acryloyloxy succinimide).

The specific features of nucleic acid -nanoparticles conjugates include:

• Enhanced Stability: Nucleic acids are susceptible to degradation by enzymes and other factors. However, once bound to nanoparticles, they generally exhibit greater stability, which protects nucleic acids from degradation and extends their functional lifetime.
• Precise delivery: Nanoparticles can be functionalized to precisely deliver nucleic acids to specific types of cells or tissues. This precise delivery is critical in applications such as gene therapy.
• Intracellular uptake: Nanoparticles can facilitate cellular uptake of nucleic acids. They can interact with cell membranes to improve the intracellular uptake of nucleic acids, thereby enhancing therapeutic or functional effects.
• High-efficiency gene delivery: In the research, it was found that the combination of nucleic acid and nanoparticles can be used for high-efficiency gene delivery. Nanoparticles protect nucleic acids during transport in the blood and help them cross cell membranes, allowing the introduced genetic material to function.
• Regulated Release: Nanoparticles can be designed to enable controlled release of nucleic acids. This regulatory release is critical in specific temporal applications of gene expression or RNA interference.
• Multifunctional platform: Nucleic acid-nanoparticle conjugates can be designed to carry multiple functional components simultaneously. For example, nanoparticles can carry therapeutic nucleic acids and imaging agents, enabling real-time monitoring of delivery and effects.
• Biocompatibility: Many nanoparticle materials used in these conjugates are designed to be biocompatible to minimize potential adverse effects when they are introduced into an organism.
• Tunable properties: The size, surface chemistry, and composition of nanoparticles can be fine-tuned to optimize their interactions with nucleic acids and target cells. This tunability enables tailoring of conjugates for specific applications.
• Self-assembly and organization: Nanoparticles are able to self-assemble with nucleic acids into organized structures, offering the potential to create novel materials with unique properties, such as enhanced optical or electronic properties.

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• Synthesis of Nucleic Acid Template Polymers

The use of DNA as a template to synthesize multifunctional nucleic acid conducting polymer nanocomposites has become an attractive application in the field of nanotechnology to enhance the performance of conducting polymers. As an authoritative expert in the field of nucleic acid polymer bioconjugation, CD Bioparticles proposed a synthetic strategy based on nucleic acid as a soft template for the preparation of polymer nanocomposites. In this approach, nucleic acid-polymer nanocomposites include, but are not limited to, polyacetylene (PA), polyaniline (PANI), polypyrrole (PPy), polythiophene (PTh), polyparaphenylene (PPP), poly Phenylene vinylene (PPV) and polyfuran (PF).

• Synthesis of Nucleic Acid Template Nanomaterials

Nucleic acids are widely used as biological templates for controlling the growth of multifunctional nanomaterials. This is because the carbonyl and amine groups on nucleic acid bases can coordinate with metal ions, while the backbone structure of phosphate can effectively prevent the irreversible aggregation of nanoparticles. In addition, DNA/RNA nanotechnology can also utilize the molecular recognition properties of nucleic acids to achieve surface modification of nanoparticles, resulting in clear 1D, 2D or 3D nanostructures. CD Bioparticles is focused on developing sophisticated nucleic acid, nucleotide and nucleobase polymer nanostructures. We provide one-stop synthesis services, including custom synthesis of RNA template nanoparticles and custom synthesis of DNA template nanoparticles.

• Nucleic Acid-Polymer Hybrid Materials

Nucleic acid-polymer hybrids have attracted great interest in the fields of science and technology because of their convenient physical mixing process driven by non-covalent interactions. The hybridization of conductive polymers to DNA has a variety of applications, including DNA hybridization sensing and nucleic acid low-potential flow detection, etc. In addition to providing custom services for conductive polymer-DNA conjugation, CD Bioparticles also offers dendrimer-DNA conjugation services, which may have important uses in non-viral gene delivery.

The applications of nucleic acid-nanoparticles conjugates include:

Linking polymers to DNA sequences often increases the stability of the DNA. This is very beneficial for this conjugate as a transcellular membrane carrier and/or a platform for multimodal medical applications. These connections find wide-ranging applications in therapeutics, precision materials, nanorobotics, ultrasensitive sensors, and molecular computers.

The field of nucleic acid polymers has been striving to integrate multiple functions (such as stimulated release, time control, and targeting) into polymer structures to enhance the biological activity and pharmacological properties of nucleic acid molecules. This has significant appeal for drug delivery and cellular imaging.

Nucleic acid-polymer complexes can exploit DNA interactions to enhance the functionality of derivatized polymers. For example, the fabrication of optoelectronic nanodevices based on DNA templates.

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References

1. Majzoub RN, et al.; Cationic liposome-nucleic acid nanoparticle assemblies with applications in gene delivery and gene silencing. Philos Trans A Math Phys Eng Sci. 2016, 374(2072):20150129.
2. Seferos DS, et al.; Locked nucleic acid-nanoparticle conjugates. Chembiochem. 2007, 8(11):1230-2.
3. Chinen AB, et al.; Spherical nucleic acid nanoparticle conjugates enhance G-quadruplex formation and increase serum protein interactions. Angew Chem Int Ed Engl. 2015, 54(2):527-31.
4. Mirkin CA, Stegh AH. Spherical nucleic acids for precision medicine. Oncotarget. 2014, 5(1):9-10.