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Introductions of Nucleic Acid‐Based Nanomaterials

Shaojingya Gao and Yunfeng Lin

Sichuan University, West China College of Stomatology, State Key Laboratory of Oral Diseases, No. 14, 3rd Sec, Ren Min Nan Road, Chengdu, 610041, PR China

Nanotechnology is a science and technology that produces substances from a single atom or molecule in a size range of 1–100 nm. As early as 1986, American scientists put forward nanotechnology in the creation of machines, but due to the low level of science and technology at that time, the technology did not achieve obvious results. Researchers believe that nanotechnology is to make the combination of molecules in a machine practical, so as to arbitrarily combine all kinds of molecules to produce different molecular structures. Nanotechnology has been extensively applied in various fields and has had a profound impact on our lives. The concept of nanotechnology was first introduced to the public in the speech “There's Plenty of Room at the Bottom” in 1960 by Nobel Prize laureate Richard P. Feynman. With the continuous development of science and technology, people's research on nanotechnology is also in‐depth, and the corresponding branch of the subject has also developed. Nanotechnology integrates quantum mechanics, molecular biology, nanobiology, nanochemistry, and other disciplines with the ultimate goal of directly constructing products with specific functions from atoms or molecules. Nanotechnology transformed the drug delivery system dramatically by delivering microtherapeutic drugs to parts of the body that are difficult to reach otherwise. With an expanding array of strategies that allow nanomaterials to tailor their properties to specific indications, nanomaterials are entering the clinic at an unprecedented rate [1]. In nanotechnology, nanomaterials are often defined as the creation of materials with new properties and functions at the nanoscale. There are two main approaches of constructing nanomaterials so far: the “top‐down” approach is to reduce the size of large structures to nanoscale, while the “bottom‐up” approach, which is also called “molecular nanotechnology,” is to engineer materials from molecular or atom components through assembly or self‐assembly. In 1953, the discovery of deoxyribonucleic acid (DNA)'s complementary base pairing principle and double helix structure ushered in the era of molecular biology. DNA became a potential material for nanofabrication due to its unique properties and high controllability [2–4]. Seeman and his coworkers first reported the synthesis rules of DNA‐based nanomaterials in the 1980s, bringing DNA nanotechnology into the limelight as a research hotspot. The most common approach to building DNA‐based nanomaterials is the “bottom‐up” approach. In recent years, DNA‐based nanomaterials have been widely used in bioimaging, biosensing, gene transfer, drug delivery, disease diagnosis, and treatment due to their inherent biodegradability and biocompatibility. In addition, DNA‐based nanomaterials are easy to customize in size and shape and have good structural stability.

DNA‐based nanomaterials come in a variety of sizes and shapes and are designed in a variety of structures, including two‐dimensional and three‐dimensional structures. According to different molecular construction methods of functional DNA‐based materials, synthetic DNA‐based nanomaterials include monolayer and multilayer nanomaterials. These DNA‐based nanomaterials can also be divided into circular, linear, and branching forms, and they have been extensively constructed and studied [5]. DNA‐based nanomaterials were commonly treated as drug delivery systems. In immunotherapy, traditional materials, including liposomes and adenoviruses, have been used as drug delivery systems in the past, but their defects limit their clinical application. For example, they share the same disadvantage of low targeting ability. Separately, adenoviruses are difficult to build and are usually toxic, while liposomes are easy to build but have low portability and low toxicity. Compared with traditional materials, DNA‐based nanomaterials have many advantages, including structural stability, unparalleled programmability, natural biocompatibility, and negligible immunogenicity. These advantages may make DNA‐based nanomaterials more favorable in immunotherapy.

DNA‐based nanomaterials with different structures are made for different biomedical purposes. With the development of DNA nanomaterials advancing, various new DNA‐based nanomaterials were constructed and widely used in immune engineering, drug delivery, molecular biology, tissue engineering, disease diagnosis or biosensing, etc. [6–18]. In recent years, successful attempts in immunotherapy have been reported, suggesting that DNA‐based nanomaterials may possess therapeutic potential. Other hyper‐polymeric compounds and nanomaterials such as avidin [19], polyethylenimine (PEI) [20–22], chitosan [23–25], and gold nanoparticles (AuNPs) [26–28] were loaded on DNA‐based nanomaterials to enhance their therapeutic effect. It has been reported in previous research that, together with other materials or specific structures, polymeric DNA‐based nanomaterials could influence the biological behavior of cells, such as proliferation [8, 9, 11, 29], autophagy [10], differentiation [30, 31], cell viability [29, 32], morphology [33], and migration [34]. Thanks to these special properties, polymeric DNA‐based nanomaterials can be potential treatments for certain diseases and applied for tissue regeneration engineering [35–37]. When combined with other materials, such as proteins and some chemical drugs, polymeric DNA‐based nanomaterials could treat some autoimmune diseases [38–41]. When combined with aptamers, the DNA‐based nanomaterials could promote the antitumor effects [29, 42, 43], the inhibition of malignant cells [42], and the ability to target [29, 32, 42]. In the past few decades, DNA‐based nanomaterials have made great progress and development, providing new options for the effective treatment of a variety of diseases and making significant contributions to the public health of society. At present, scientists have developed a variety of delivery systems, such as DNA origami, DNA tiles, and tetrahedral DNA‐based nanomaterials (TDNs). In this chapter, we will make a summary of the self‐assembly and structural design of DNA‐based nanomaterials and highlight their therapeutic potential in immunotherapy.

1.1 History of DNA‐Based Nanomaterials – Design and Construction

Nucleic acid is a biological macromolecule used by living organisms to store genetic information [4, 44]. Being the basic genetic material in nature, it is not only closely related to normal life activities such as growth and reproduction, genetic variation, and cell differentiation but also closely related to abnormal life activities such as the occurrence of tumor, radiation damage, genetic disease, metabolic disease, viral infection, and so on. Moreover, nucleic acids have many unique properties besides their biological function; their molecular recognition ability, biocompatibility, and controllability at the nanoscale contribute to the construction of a variety of complex inorganic and organic nanostructures. Therefore, the study of nucleic acids is an important field in the development of modern biochemistry, molecular biology, and medicine. Nucleic acids are usually found in cells in the form of nucleoproteins that bind to proteins. Natural nucleic acids are divided into two main groups, namely ribonucleic acid (RNA) and DNA. The high controllability and high precision of Watson–Crick base pairing made DNA‐based nanomaterials a potential substance for nanofabrication [2–4, 45]. Through the process of self‐assembly, a large number of DNA‐based nanomaterials of different shapes and sizes have been designed and constructed based on the classical Watson–Crick base pairing principle. Some DNA‐based nanomaterials can change the biological behavior of cells functionally, such as cell migration, cell proliferation, cell differentiation, autophagy, and anti‐inflammatory effects; hence, DNA nanotechnology has been greatly developed. DNA‐based nanomaterials are employed in different scientific directions for various biological applications such as tissue regeneration, disease prevention, inflammation inhibition, bioimaging, biosensing, diagnosis, antitumor drug delivery, and therapeutics. In this section, we hope to introduce you to a comprehensive history of DNA‐based nanomaterials.

The era of molecular biology began in 1953 with the discovery of the principle of complementary base pairing and the double helix structure of DNA. Ever since then research on the genetic function of DNA at the microlevel has become a hot topic. In the year of 1990s, further research sparked new interest in nongenetic functions among nucleic acid researchers, prompting scientists to further investigate. The first discovered...