Schematics of DNA nanotube folding, modifications, and drug loading. (A) DNA nanotube self-assembly (schematically) using the single-stranded tile method. Five DNA strands form DNA double-crossover tiles. A DNA tile is formed with four short single-stranded sections called sticky ends (marked a, b, a′, and b′) that act as binding domains. Individual helical domains are connected by interhelix crossovers. Each domain is complementary to one domain of neighboring tiles and several domains hybridized with each other to form nanotubes (the single-stranded tile method of assembly of DNA nanotube). This interaction is provided due to complementary interactions of their sticky ends. Tiles can be schematically represented as molecular bricks with complementary connectors. The sticky end arrangement directs the hybridization of DNA tiles to form tubular DNA structures with a range of diameters. Their distribution is determined by the thermodynamics and kinetics of the DNA nanotube assembly process. (B) Modifications of DNA nanotubes: linker (CpG, cholesterol, aptamers, etc.); nanoparticles (Au); chemotherapy or photodynamic therapy drug; other ligands.