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Functional DNA-containing nanomaterials: cellular applications in biosensing, imaging, and targeted therapy.

Liang H, Zhang XB, Lv Y, Gong L, Wang R, Zhu X, Yang R, Tan W - Acc. Chem. Res. (2014)

Bottom Line: Under proper conditions, multiple ligand-receptor interactions, decreased steric hindrance, and increased surface roughness can be achieved from a high density of DNA that is bound to the surface of nanomaterials, resulting in a higher affinity for complementary DNA and other targets.For example, DNAzymes assembled on gold nanoparticles can effectively catalyze chemical reactions even in living cells.For example, gold nanoparticles and graphene oxides can quench fluorescence efficiently to achieve low background and effectively increase the signal-to-background ratio.

View Article: PubMed Central - PubMed

Affiliation: Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center of Molecular Engineering for Theranostics, Hunan University , Changsha, Hunan 410082, China.

ABSTRACT
CONSPECTUS: DNA performs a vital function as a carrier of genetic code, but in the field of nanotechnology, DNA molecules can catalyze chemical reactions in the cell, that is, DNAzymes, or bind with target-specific ligands, that is, aptamers. These functional DNAs with different modifications have been developed for sensing, imaging, and therapeutic systems. Thus, functional DNAs hold great promise for future applications in nanotechnology and bioanalysis. However, these functional DNAs face challenges, especially in the field of biomedicine. For example, functional DNAs typically require the use of cationic transfection reagents to realize cellular uptake. Such reagents enter the cells, increasing the difficulty of performing bioassays in vivo and potentially damaging the cell's nucleus. To address this obstacle, nanomaterials, such as metallic, carbon, silica, or magnetic materials, have been utilized as DNA carriers or assistants. In this Account, we describe selected examples of functional DNA-containing nanomaterials and their applications from our recent research and those of others. As models, we have chosen to highlight DNA/nanomaterial complexes consisting of gold nanoparticles, graphene oxides, and aptamer-micelles, and we illustrate the potential of such complexes in biosensing, imaging, and medical diagnostics. Under proper conditions, multiple ligand-receptor interactions, decreased steric hindrance, and increased surface roughness can be achieved from a high density of DNA that is bound to the surface of nanomaterials, resulting in a higher affinity for complementary DNA and other targets. In addition, this high density of DNA causes a high local salt concentration and negative charge density, which can prevent DNA degradation. For example, DNAzymes assembled on gold nanoparticles can effectively catalyze chemical reactions even in living cells. And it has been confirmed that DNA-nanomaterial complexes can enter cells more easily than free single-stranded DNA. Nanomaterials can be designed and synthesized in needed sizes and shapes, and they possess unique chemical and physical properties, which make them useful as DNA carriers or assistants, excellent signal reporters, transducers, and amplifiers. When nanomaterials are combined with functional DNAs to create novel assay platforms, highly sensitive biosensing and high-resolution imaging result. For example, gold nanoparticles and graphene oxides can quench fluorescence efficiently to achieve low background and effectively increase the signal-to-background ratio. Meanwhile, gold nanoparticles themselves can be colorimetric reporters because of their different optical absorptions between monodispersion and aggregation. DNA self-assembled nanomaterials contain several properties of both DNA and nanomaterials. Compared with DNA-nanomaterial complexes, DNA self-assembled nanomaterials more closely resemble living beings, and therefore they have lower cytotoxicity at high concentrations. Functional DNA self-assemblies also have high density of DNA for multivalent reaction and three-dimensional nanostructures for cell uptake. Now and in the future, we envision the use of DNA bases in making designer molecules for many challenging applications confronting chemists. With the further development of artificial DNA bases using smart organic synthesis, DNA macromolecules based on elegant molecular assembly approaches are expected to achieve great diversity, additional versatility, and advanced functions.

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Designof a fluorescent DNAzyme immobilized on AuNPs as a selective probeof uranyl inside live cells. Reproduced with permission from ref (32). Copyright 2013 AmericanChemical Society.
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fig7: Designof a fluorescent DNAzyme immobilized on AuNPs as a selective probeof uranyl inside live cells. Reproduced with permission from ref (32). Copyright 2013 AmericanChemical Society.

Mentions: AuNP–DNA conjugates are stable in serum and can enter cellswithout transfection reagents. Based on their special electronic properties,AuNPs display “superquenching” ability for fluorescencevia long-range resonance energy transfer.29 The Mirkin group reported aptamer–AuNP complexes, termedaptamer nanoflares, and detected intracellular ATP levels.30 DNA polymers assembled on AuNPs can be variouslydesigned, for example by labeling with imaging fluorescent tags orthe simultaneous loading of recognition elements and anticancer drugs.31 The AuNP–DNA conjugates show high stabilityand good biocompatibility, and the size of the complex can be controlledby changing the length of the self-assembled DNA biopolymer shell,which might provide a new and highly effective means for transportingcargos. Recently, the Lu group developed a novel DNAzyme–goldnanoparticle probe, which, for the first time, could be successfullyapplied to detect target analytes in living cells.32 The 39E DNAzyme, which has exceptional selectivity andsensitivity for the uranyl ion (UO22+), waschosen as an initial demonstration, and AuNP was chosen to be thecarrier for cellular delivery of the DNAzyme. The assembly strategyof this novel system is shown in Figure 7.In the presence of uranyl, cleavage of the fluorophore-labeled substratestrand is catalyzed by DNAzyme. The shorter product strand labeledwith Cy3 is released, and fluorescence is simultaneously recovered.Subsequently, this DNAzyme–AuNP probe was demonstrated to easilyenter cells and serve as a metal ion sensor in the cellular environment.


Functional DNA-containing nanomaterials: cellular applications in biosensing, imaging, and targeted therapy.

Liang H, Zhang XB, Lv Y, Gong L, Wang R, Zhu X, Yang R, Tan W - Acc. Chem. Res. (2014)

Designof a fluorescent DNAzyme immobilized on AuNPs as a selective probeof uranyl inside live cells. Reproduced with permission from ref (32). Copyright 2013 AmericanChemical Society.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4066909&req=5

fig7: Designof a fluorescent DNAzyme immobilized on AuNPs as a selective probeof uranyl inside live cells. Reproduced with permission from ref (32). Copyright 2013 AmericanChemical Society.
Mentions: AuNP–DNA conjugates are stable in serum and can enter cellswithout transfection reagents. Based on their special electronic properties,AuNPs display “superquenching” ability for fluorescencevia long-range resonance energy transfer.29 The Mirkin group reported aptamer–AuNP complexes, termedaptamer nanoflares, and detected intracellular ATP levels.30 DNA polymers assembled on AuNPs can be variouslydesigned, for example by labeling with imaging fluorescent tags orthe simultaneous loading of recognition elements and anticancer drugs.31 The AuNP–DNA conjugates show high stabilityand good biocompatibility, and the size of the complex can be controlledby changing the length of the self-assembled DNA biopolymer shell,which might provide a new and highly effective means for transportingcargos. Recently, the Lu group developed a novel DNAzyme–goldnanoparticle probe, which, for the first time, could be successfullyapplied to detect target analytes in living cells.32 The 39E DNAzyme, which has exceptional selectivity andsensitivity for the uranyl ion (UO22+), waschosen as an initial demonstration, and AuNP was chosen to be thecarrier for cellular delivery of the DNAzyme. The assembly strategyof this novel system is shown in Figure 7.In the presence of uranyl, cleavage of the fluorophore-labeled substratestrand is catalyzed by DNAzyme. The shorter product strand labeledwith Cy3 is released, and fluorescence is simultaneously recovered.Subsequently, this DNAzyme–AuNP probe was demonstrated to easilyenter cells and serve as a metal ion sensor in the cellular environment.

Bottom Line: Under proper conditions, multiple ligand-receptor interactions, decreased steric hindrance, and increased surface roughness can be achieved from a high density of DNA that is bound to the surface of nanomaterials, resulting in a higher affinity for complementary DNA and other targets.For example, DNAzymes assembled on gold nanoparticles can effectively catalyze chemical reactions even in living cells.For example, gold nanoparticles and graphene oxides can quench fluorescence efficiently to achieve low background and effectively increase the signal-to-background ratio.

View Article: PubMed Central - PubMed

Affiliation: Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center of Molecular Engineering for Theranostics, Hunan University , Changsha, Hunan 410082, China.

ABSTRACT
CONSPECTUS: DNA performs a vital function as a carrier of genetic code, but in the field of nanotechnology, DNA molecules can catalyze chemical reactions in the cell, that is, DNAzymes, or bind with target-specific ligands, that is, aptamers. These functional DNAs with different modifications have been developed for sensing, imaging, and therapeutic systems. Thus, functional DNAs hold great promise for future applications in nanotechnology and bioanalysis. However, these functional DNAs face challenges, especially in the field of biomedicine. For example, functional DNAs typically require the use of cationic transfection reagents to realize cellular uptake. Such reagents enter the cells, increasing the difficulty of performing bioassays in vivo and potentially damaging the cell's nucleus. To address this obstacle, nanomaterials, such as metallic, carbon, silica, or magnetic materials, have been utilized as DNA carriers or assistants. In this Account, we describe selected examples of functional DNA-containing nanomaterials and their applications from our recent research and those of others. As models, we have chosen to highlight DNA/nanomaterial complexes consisting of gold nanoparticles, graphene oxides, and aptamer-micelles, and we illustrate the potential of such complexes in biosensing, imaging, and medical diagnostics. Under proper conditions, multiple ligand-receptor interactions, decreased steric hindrance, and increased surface roughness can be achieved from a high density of DNA that is bound to the surface of nanomaterials, resulting in a higher affinity for complementary DNA and other targets. In addition, this high density of DNA causes a high local salt concentration and negative charge density, which can prevent DNA degradation. For example, DNAzymes assembled on gold nanoparticles can effectively catalyze chemical reactions even in living cells. And it has been confirmed that DNA-nanomaterial complexes can enter cells more easily than free single-stranded DNA. Nanomaterials can be designed and synthesized in needed sizes and shapes, and they possess unique chemical and physical properties, which make them useful as DNA carriers or assistants, excellent signal reporters, transducers, and amplifiers. When nanomaterials are combined with functional DNAs to create novel assay platforms, highly sensitive biosensing and high-resolution imaging result. For example, gold nanoparticles and graphene oxides can quench fluorescence efficiently to achieve low background and effectively increase the signal-to-background ratio. Meanwhile, gold nanoparticles themselves can be colorimetric reporters because of their different optical absorptions between monodispersion and aggregation. DNA self-assembled nanomaterials contain several properties of both DNA and nanomaterials. Compared with DNA-nanomaterial complexes, DNA self-assembled nanomaterials more closely resemble living beings, and therefore they have lower cytotoxicity at high concentrations. Functional DNA self-assemblies also have high density of DNA for multivalent reaction and three-dimensional nanostructures for cell uptake. Now and in the future, we envision the use of DNA bases in making designer molecules for many challenging applications confronting chemists. With the further development of artificial DNA bases using smart organic synthesis, DNA macromolecules based on elegant molecular assembly approaches are expected to achieve great diversity, additional versatility, and advanced functions.

Show MeSH