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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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(A) Schematic illustration of aptamer–micelle formation. (B)Flow cytometric assay to monitor the binding of free TDO5 (250 nM)with Ramos cells (target cells) and HL60 (control cells) at 37 °Cfor 5 min. The blue and black curves represent the background bindingof unselected DNA library or library–micelle. The purple andred curves represent the binding of TDO5 or TDO5–micelle. Reproducedwith permission from ref (28). Copyright 2010 National Academy of Sciences.
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fig6: (A) Schematic illustration of aptamer–micelle formation. (B)Flow cytometric assay to monitor the binding of free TDO5 (250 nM)with Ramos cells (target cells) and HL60 (control cells) at 37 °Cfor 5 min. The blue and black curves represent the background bindingof unselected DNA library or library–micelle. The purple andred curves represent the binding of TDO5 or TDO5–micelle. Reproducedwith permission from ref (28). Copyright 2010 National Academy of Sciences.

Mentions: Inspired by amphiphilic blockcopolymers, which can self-assemble into different morphologies, thecopolymer that contains a hydrophilic DNA segment and a hydrophobicorganic polymer unit can form a DNA micelle under certain conditions.Compared with DNA-conjugated nanoparticles, DNA micelles have no inorganiccores, which would be cytotoxic at high concentrations, and the timerequired to synthesize DNA micelles can generally be abbreviated.In order to endow DNA micelles with more applicable properties andfunctions, we chose an aptamer to replace general DNA and conjugatedit with a hydrophobic lipid tail. In 2010, we demonstrated that theaptamers in aptamer–micelle conjugates could still recognizetheir specific targets.28 Figure 6 shows that aptamer TDO5 was unable to bind withRamos cells at physiological temperature. However, the TDO5–micelleconjugate displayed high affinity and selectivity for its target Ramoscells, as a result of densely packed aptamers that could enhance affinityfor the target.


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)

(A) Schematic illustration of aptamer–micelle formation. (B)Flow cytometric assay to monitor the binding of free TDO5 (250 nM)with Ramos cells (target cells) and HL60 (control cells) at 37 °Cfor 5 min. The blue and black curves represent the background bindingof unselected DNA library or library–micelle. The purple andred curves represent the binding of TDO5 or TDO5–micelle. Reproducedwith permission from ref (28). Copyright 2010 National Academy of Sciences.
© Copyright Policy
Related In: Results  -  Collection

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

fig6: (A) Schematic illustration of aptamer–micelle formation. (B)Flow cytometric assay to monitor the binding of free TDO5 (250 nM)with Ramos cells (target cells) and HL60 (control cells) at 37 °Cfor 5 min. The blue and black curves represent the background bindingof unselected DNA library or library–micelle. The purple andred curves represent the binding of TDO5 or TDO5–micelle. Reproducedwith permission from ref (28). Copyright 2010 National Academy of Sciences.
Mentions: Inspired by amphiphilic blockcopolymers, which can self-assemble into different morphologies, thecopolymer that contains a hydrophilic DNA segment and a hydrophobicorganic polymer unit can form a DNA micelle under certain conditions.Compared with DNA-conjugated nanoparticles, DNA micelles have no inorganiccores, which would be cytotoxic at high concentrations, and the timerequired to synthesize DNA micelles can generally be abbreviated.In order to endow DNA micelles with more applicable properties andfunctions, we chose an aptamer to replace general DNA and conjugatedit with a hydrophobic lipid tail. In 2010, we demonstrated that theaptamers in aptamer–micelle conjugates could still recognizetheir specific targets.28 Figure 6 shows that aptamer TDO5 was unable to bind withRamos cells at physiological temperature. However, the TDO5–micelleconjugate displayed high affinity and selectivity for its target Ramoscells, as a result of densely packed aptamers that could enhance affinityfor the target.

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