Functional Nucleic Acid Nanomaterials: Development, Properties, and Applications.

Functional nucleic acid (FNA) nanotechnology is an interdisciplinary field between nucleic acid biochemistry and nanotechnology that focuses on the study of interactions between FNAs and nanomaterials and explores the particular advantages and applications of FNA nanomaterials. With the goal of building the next-generation biomaterials that combine the advantages of FNAs and nanomaterials, the interactions between FNAs and nanomaterials as well as FNA self-assembly technologies have established themselves as hot research areas, where the target recognition, response, and self-assembly ability, combined with the plasmon properties, stability, stimuli-response, and delivery potential of various nanomaterials can give rise to a variety of novel fascinating applications. As research on the structural and functional group features of FNAs and nanomaterials rapidly develops, many laboratories have reported numerous methods to construct FNA nanomaterials. In this Review, we first introduce some widely used FNAs and nanomaterials along with their classification, structure, and application features. Then we discuss the most successful methods employing FNAs and nanomaterials as elements for creating advanced FNA nanomaterials. Finally, we review the extensive applications of FNA nanomaterials in bioimaging, biosensing, biomedicine, and other important fields, with their own advantages and drawbacks, and provide our perspective about the issues and developing trends in FNA nanotechnology.

Xu W ，He W ，Du Z ，Zhu L ，Huang K ，Lu Y ，Luo Y ... -  《-》

Molecular Engineering of Functional Nucleic Acid Nanomaterials toward In Vivo Applications.

Recent advances in nanotechnology and engineering have generated many nanomaterials with unique physical and chemical properties. Over the past decade, numerous nanomaterials are introduced into many research areas, such as sensors for environmental monitoring, food safety, point-of-care diagnostics, and as transducers for solar energy transfer. Meanwhile, functional nucleic acids (FNAs), including nucleic acid enzymes, aptamers, and aptazymes, have attracted major attention from the biomedical community due to their unique target recognition and catalytic properties. Benefiting from the recent progress of molecular engineering strategies, the physicochemical properties of nanomaterials are endowed by the target recognition and catalytic activity of FNAs in the presence of a target analyte, resulting in numerous smart nanoprobes for diverse applications including intracellular imaging, drug delivery, in vivo imaging, and tumor therapy. This progress report focuses on the recent advances in designing and engineering FNA-based nanomaterials, highlighting the functional outcomes toward in vivo applications. The challenges and opportunities for the future translation of FNA-based nanomaterials into clinical applications are also discussed.

Zhang J ，Lan T ，Lu Y 《-》

Metal ion detection using functional nucleic acids and nanomaterials.

Metal ion detection is critical in a variety of areas. The past decade has witnessed great progress in the development of metal ion sensors using functional nucleic acids (FNAs) and nanomaterials. The former has good recognition selectivity toward metal ions and the latter possesses unique properties for enhancing the performance of metal ion sensors. This review offers a summary of FNA- and nanomaterial-based metal ion detection methods. FNAs mainly include DNAzymes, G-quadruplexes, and mismatched base pairs and nanomaterials cover gold nanoparticles (GNPs), quantum dots (QDs), carbon nanotubes (CNTs), and graphene oxide (GO). The roles of FNAs and nanomaterials are introduced first. Then, various methods based on the combination of different FNAs and nanomaterials are discussed. Finally, the challenges and future directions of metal ion sensors are presented.

Huang J ，Su X ，Li Z 《-》

Construction of rolling circle amplification products-based pure nucleic acid nanostructures for biomedical applications.

Nucleic acid nanomaterials with good biocompatibility, biodegradability, and programmability have important applications in biomedical field. Nucleic acid nanomaterials are usually combined with some inorganic nanomaterials to improve their biological stability. However, undefined toxic side effects of composite nanocarriers hamper their application in vivo. As a nanotool capable of avoiding potential biotoxicity, nanostructures composed entirely of DNA oligonucleotides have been rapidly developed in the field of biomedicine in recent years. Rolling circle amplification (RCA) is an isothermal enzymatic nucleic acid amplification technology for large-scale production of periodic DNA/RNA with pre-designed desirable structures and functions. RCA products with different functional parts can be customized by changing the sequence of the circular template, thereby generating complex multifunctional DNA nanostructures, such as DNA nanowire, nanoflower, origami, nanotube, nanoribbon, etc. More importantly, RCA products as nonnicked building blocks can enhance the biostability of DNA nanostructures, especially in vivo. These RCA products-based nucleic acid nanostructures can be used as scaffolds or nanocarriers to interact or load with metal nanoparticles, proteins, lipids, cationic polymers, therapeutic nucleic acids or drugs, etc. This paper reviews the assembly strategies of RCA based DNA nanostructures with different shape and their applications in biosensing, bioimaging and biomedicine. Finally, the development prospects of the nucleic acid nanomaterials in clinical diagnosis and treatment of diseases are described. STATEMENT OF SIGNIFICANCE: As a nanotool capable of avoiding potential biotoxicity, nanostructures composed entirely of DNA oligonucleotides have been rapidly developed in the field of biomedicine in recent years. Rolling circle amplification (RCA) is an isothermal enzymatic nucleic acid amplification technology for large-scale production of periodic DNA/RNA with pre-designed desirable structures and functions. This paper reviews the construction of various shapes of pure nucleic acid nanomaterials based on RCA products and their applications in biosensing, bioimaging and biomedicine. This will promote the development of biocompatible DNA nanovehicles and their further application in living systems, including bioimaging, molecular detection, disease diagnosis and drug delivery, finally producing a significant impact in the field of nanotechnology and nanomedicine.

Li C ，Wang Y ，Li PF ，Fu Q ... -  《-》

Framework Nucleic Acids in Nuclear Medicine Imaging: Shedding Light on Nano-Bio Interactions.

Framework nucleic acids (FNAs) represent nanoscale oligonucleotide assemblies with unique physical, chemical, and biological properties that are different from their building blocks. Following simple Watson-Crick base-pairing rules, arbitrary DNA frameworks with diverse shapes, sizes, and dimensions can be prepared with high reproducibility and stability. The programmable assembly of nucleic acids into FNAs presents a highly controllable model for studies on nano-bio interactions and allows scrutiny of "nanostructure-activity relationships." Herein, we present an overview of recent progress with FNAs in the hope of deepening our understanding of nano-bio interfacing. We summarize the biological profiles and immune responses of various FNAs as functions of their shape, sizes, and surface charges. We then highlight recent efforts to apply FNAs for biomedical applications and discuss the challenges of FNAs for potential clinical translation. We believe that this Minireview can bring up-to-date information on FNAs and shed light on how their design may be harnessed for selective biomedical applications.

Wang H ，Liu Q ，Lan X ，Jiang D ... -  《-》