Current Drug Metabolism - Volume 24, Issue 5, 2023

Nucleic acid strands can be synthesized into various nucleic acid-based nanomaterials (NANs) through strict base pairing. The self-assembled NANs are programmable, intelligent, biocompatible, non-immunogenic, and non-cytotoxic. With the rapid development of nanotechnology, the application of NANs in the biomedical fields, such as drug delivery and biological sensing, has attracted wide attention. However, the stability of NANs is often affected by the cation concentrations, enzymatic degradation, and organic solvents. This susceptibility to degradation is one of the most important factors that have restricted the application of NANs. NANs can be denatured or degraded under conditions of low cation concentrations, enzymatic presence, and organic solvents. To deal with this issue, a lot of methods have been attempted to improve the stability of NANs, including artificial nucleic acids, modification with specific groups, encapsulation with protective structures, etc. In this review, we summarized the relevant methods to have a deeper understanding of the stability of NANs.

Deoxyribonucleic acid (DNA), as a natural polymer material, carries almost all the genetic information and is recognized as one of the most intelligent natural polymers. In the past 20 years, there have been many exciting advances in the synthesis of hydrogels using DNA as the main backbone or cross-linking agent. Different methods, such as physical entanglement and chemical cross-linking, have been developed to perform the gelation of DNA hydrogels. The good designability, biocompatibility, designable responsiveness, biodegradability and mechanical strength provided by DNA building blocks facilitate the application of DNA hydrogels in cytoscaffolds, drug delivery systems, immunotherapeutic carriers, biosensors and nanozyme-protected scaffolds. This review provides an overview of the main classification and synthesis methods of DNA hydrogels and highlights the application of DNA hydrogel in biomedical fields. It aims to give readers a better understanding of DNA hydrogels and development trends.

Osteoarthritis (OA) involves lesions of the entire joint and remains one of the health problems plaguing the world. The pathological mechanism of OA is complex and involves multiple signaling pathways. Over 300 million people worldwide are living with OA, which imposes a huge burden on society. Nucleic acid nanomaterials are of interest to the biomedical field due to their small dimension, ideal biocompatibility, and structure editability. Various nucleic acids have been used as therapeutic drugs to regulate the pathogenesis and development of OA. Among them, some can enter the cell by themselves and others with the aid of vectors. Apart from high therapeutic efficiency, nucleic acid nanomaterials also act as carriers for transporting drugs. This paper reviews recent advances in nucleic acid nanomaterials in OA therapy, suggesting that nucleic acid nanomaterials-based therapy has good prospects for development.

Framework nucleic acids (FNAs), which are a series of self-assembled DNA nanostructures, are highly versatile tools for engineering intelligent molecular delivery vehicles. Owing to their precise and controllable design and construction, excellent programmability and functionality, as well as favorable intercalation between DNA and small molecules, FNAs provide a promising approach for small molecule delivery. This review discusses the advantages, applications, and current challenges of FNAs for the delivery of small molecular cargo. First, the physicochemical and biological properties that make FNAs favorable for the transport of small molecules are introduced. Thereafter, the classification of loaded cargos and the mechanism of combination between small molecules and FNAs are summarized in detail, and recent research on FNA-based delivery systems and their applications are highlighted. Finally, the challenges and prospects of FNA nanocarriers are discussed to advance their exploitation and clinical adoption.

Background: Nucleic acid is a genetic material that shows great potential in a variety of biological applications. With the help of nanotechnology, the fabrication of DNA-based nanomaterials has emerged. From genetic DNA to non-genetic functional DNA, from single-layer and flat structure to multi-layer and complex structure, and from two-dimensional to three-dimensional structure, DNA-based nanomaterials have been greatly developed, bringing significant changes to our lives. In recent years, the research of DNA-based nanomaterials for biological applications has developed rapidly. Methods: We extensively searched the bibliographic database for a research article on nanotechnology and immunotherapy and further discussed the advantages and drawbacks of current DNA-based nanomaterials in immunotherapy. By comparing DNA-based nanomaterials with traditional biomaterials applied in immunotherapy, we found that DNA-based nanomaterials are a promising candidate material in Immunotherapy. Results: Due to the unrivaled editability and biocompatibility, DNA-based nanomaterials are not only investigated as therapeutic particles to influence cell behavior but also as drug delivery systems to treat a variety of diseases. Moreover, when DNA-based nanomaterials are loaded with therapeutic agents, including chemical drugs and biomolecules, which significantly enhance the therapeutic effects, DNA-based nanomaterials have great potential in immunotherapy. Conclusion: This review summarizes the structural development history of DNA-based nanomaterials and their biological applications in immunotherapy, including the potential treatment of cancer, autoimmune diseases, and inflammatory diseases.

Endocrine and metabolic diseases are the most prevalent chronic diseases globally, posing the greatest hazard to human health. Although various medications are applied in treating endocrine and metabolic illnesses, numerous obstacles exist to overcome. Nucleic acid nanomaterials are novel materials synthesized and engineered in the laboratory. In this case, Nucleic acids are employed as non-biological nanomaterials instead of serving as carriers of genetic information in live cells. Because of their high biocompatibility and editability, nucleic acid nanomaterials were frequently employed in disease diagnosis and therapy. In this review, recent developments and new viewpoints on nucleic acid nanomaterials are highlighted in the fields of diabetes mellitus and other endocrine and metabolic diseases.

Mitochondrial dysfunction is considered highly related to the development and progression of diseases, including cancer, metabolism disturbance, and neurodegeneration. Traditional pharmacological approach for mitochondrial dysfunction treatment has off-target and dose-dependent side effects, which leads to the emergence of mitochondrial gene therapy by regulating coding or noncoding genes by using nucleic acid sequences such as oligonucleotides, peptide nucleic acids, rRNA, siRNA, etc. To avoid size heterogeneity and potential cytotoxicity of the traditional delivery vehicle like liposome, framework nucleic acids have shown promising potentials. First, special spatial structure like tetrahedron allows entry into cells without transfection reagents. Second, the nature of nucleic acid provides the editability of framework structure, more sites and methods for drug loading and targeted sequences linking, providing efficient transportation and accurate targeting to mitochondria. Third, controllable size leads a possibility to go through biological barrier such as the blood-brain barrier, reaching the central nervous system to reverse mitochondria-related neurodegeneration. In addition, it's biocompatibility and physiological environmental stability open up the possibility of in vivo treatments for mitochondrial dysfunction. Furthermore, we discuss the challenges and opportunities of framework nucleic acids-based delivery systems in mitochondrial dysfunction.