ABSTRACT
DNA origami is a cutting-edge DNA self-assembly technique that neatly folds DNA strands and creates specific structures based on the complementary base pairing principle. These innovative DNA origami nanostructures provide numerous benefits, including lower biotoxicity, increased stability, and superior adaptability, making them an excellent choice for transporting anti-tumor agents. Furthermore, they can considerably reduce side effects and improve therapy success by offering precise, targeted, and multifunctional drug delivery system. This comprehensive review looks into the principles and design strategies of DNA origami, providing valuable insights into this technology's latest research achievements and development trends in the field of anti-tumor drug delivery. Additionally, we review the key function and major benefits of DNA origami in cancer treatment, some of these approaches also involve aspects related to DNA tetrahedra, aiming to provide novel ideas and effective solutions to address drug delivery challenges in cancer therapy.
ABSTRACT
DNA nanostructures possess unique programmability and addressability and exhibit a wide variety of potential applications. Recently, they demonstrated their ability to be ideal carriers of antibacterial drugs. In this study, the first use of a DNA six-helix bundle (6HB) nanostructure to co-deliver antisense oligonucleotide (ASO) and silver ions is reported. Although 6HB with Ag+ shows excellent antibacterial effect against both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus, 6HB with ASO selectively inhibits S. aureus. Furthermore, 6HB with both Ag+ and ASO exhibits enhanced antibacterial efficacy on S. aureus, probably through two sequential activities. Specifically, Ag+-modified 6HB greatly delays bacterial growth by destroying its cell walls, whereas 6HB conjugated with ASO targeting the ftsZ gene of S. aureus effectively inhibits its growth in the logarithmic growth phase by inhibiting the expression of the ftsZ gene. Moreover, this synergistic antibacterial treatment shows excellent biosafety with human normal liver cell L02. This co-delivery system by DNA nanostructures provides a promising platform for antibacterial therapeutics.
Subject(s)
Anti-Bacterial Agents/pharmacology , DNA/chemistry , Drug Carriers/chemistry , Nanostructures/chemistry , Oligonucleotides, Antisense/pharmacology , Silver/pharmacology , Escherichia coli/drug effects , Microbial Sensitivity Tests , Nucleic Acid Conformation , Staphylococcus aureus/drug effectsABSTRACT
As a milestone in DNA self-assembly, DNA origami has demonstrated powerful applications in many fields. However, the scarce availability of long single-stranded DNA (ssDNA) limits the size and sequences of DNA origami nanostructures, which in turn impedes the further development. In this study, we present a robust strategy to produce long circular ssDNA scaffold strands with custom-tailored lengths and sequences. These ssDNA products were then used as scaffolds for constructing various DNA origami nanostructures. This scalable method produces ssDNA at low cost with high purity and high yield, which can enable production of custom-designed DNA origami for various applications.
Subject(s)
DNA/chemistry , DNA, Single-Stranded , Nanostructures , Nanotechnology , Nucleic Acid ConformationABSTRACT
Low molecular weight (1.8 kDa) branched polyethylenimine (PEI) has been used as non-viral vector for gene delivery because of its low toxicity, however, its further application in biomedical field has been restricted due to its low gene transfection efficiency. Herein, ZnO microflowers were prepared to increase the gene expression level mediated by PEI. Four methods have been applied to tune the shape of ZnO microstructures. Scanning electron microscopy (SEM) demonstrated the successful preparation of four kinds of flower like ZnO microparticles. By loading PEI/pDNA into ZnO microparticles, the formed new complexes showed enhanced gene transfection compared to PEI/pDNA alone. Cell uptaking experiments explained a possible mechanism that the tips of ZnO microflowers penetrated into the surface of cells, thus facilitating the entry of gene cargo into cells. These findings highlight the potential of needle like microstructure as adjuvant for efficient biomacromolecular delivery.
Subject(s)
Gene Transfer Techniques , Metal Nanoparticles/chemistry , Polyethyleneimine/chemistry , Zinc Oxide/chemistry , Cell Death , Cell Survival , DNA/metabolism , Electrophoresis, Agar Gel , Endocytosis , HeLa Cells , Humans , Molecular Weight , Plasmids , Transfection , X-Ray DiffractionABSTRACT
Cationic liposomes have been widely used as efficient gene carriers. However, the serious cytotoxicity caused by exposed positive charges restricts the further application of those kinds of gene vectors. Thus, it is challenging to develop biocompatiable non-positive charge carriers to achieve high gene transfection efficiencies. Herein, we report a novel design by pasting biocompatible anionic polyelectrolyte, namely alginic acid, hyaluronic acid, pectin and polyglutamic acid, to the positive charge surface of liposome/pDNA complex. Through shielding the positive charges, the new gene carriers show decreased cytotoxicity while still maintaining high transfection efficiency. To be noted, the complex formed by coating polyglutamic acid to the surface of liposome/pDNA greatly enhanced the transfection efficiency in HepG2 cells, and the use of pectin shows increased transfection in MCF-7 cells. Hemolysis assay proved a possible mechanism that when the new gene complex was internalized into cells, as acidity increases, more side chains become hydrophobic, and thus destabilizing the endosomal membrane to accelerate DNA escape. The present results suggest that such anionic polyelectrolyte covered liposome based carrier possess promising application for clinical gene delivery.
