Functional DNA-containing nanomaterials: cellular applications in biosensing, imaging, and targeted therapy.
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.
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.
Hao
H
Liang
Xiao-Bing
XB
Zhang
Yifan
Y
Lv
Liang
L
Gong
Ruowen
R
Wang
Xiaoyan
X
Zhu
Ronghua
R
Yang
Weihong
W
Tan
D015374:Biosensing Techniques / Q000379:methods*; D002244:Carbon / Q000737:chemistry; D002384:Catalysis; D003124:Colorimetry; D004247:DNA / Q000737:chemistry*; D004277:DNA, Single-Stranded; D003952:Diagnostic Imaging / Q000379:methods*; D016503:Drug Delivery Systems; D006108:Graphite; D006801:Humans; D058185:Magnetite Nanoparticles; D058990:Molecular Targeted Therapy / Q000379:methods*; D049329:Nanostructures / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods
D004277:DNA, Single-Stranded; D058185:Magnetite Nanoparticles; D002244:Carbon; D006108:Graphite; D004247:DNA