Over the past decade, we have seen rapid advances in applying nanotechnology in biomedical areas including bioimaging, biodetection, and drug delivery. As an emerging field, DNA nanotechnology offers simple yet powerful design techniques for self-assembly of nanostructures with unique advantages and high potential in enhancing drug targeting and reducing drug toxicity. Various sequence programming and optimization approaches have been developed to design DNA nanostructures with precisely engineered, controllable size, shape, surface chemistry, and function. Potent anticancer drug molecules, including Doxorubicin and CpG oligonucleotides, have been successfully loaded on DNA nanostructures to increase their cell uptake efficiency. These advances have implicated the bright future of DNA nanotechnology-enabled nanomedicine. In this review, we begin with the origin of DNA nanotechnology, followed by summarizing state-of-the-art strategies for the construction of DNA nanostructures and drug payloads delivered by DNA nanovehicles. Further, we discuss the cellular fates of DNA nanostructures as well as challenges and opportunities for DNA nanostructure-based drug delivery.

Bacteria-infected wounds are attracting increasing attention, as antibiotic misuse and multidrug-resistant bacteria complicate their treatment. Herein, we reported a photothermal activity-based drug consisting of β-cyclodextrin (βCD)-functionalized graphene oxide (GO) near-infrared light-responsive nanovehicles combined with the nitric oxide donor BNN6, in a methacrylate-modified gelatin (GelMA)/ hyaluronic acid graft dopamine (HA-DA) hydrogel. The synergistic effects of photothermal and gas therapies are expected to improve antibacterial efficiency and reduce drug resistance. The results revealed that GelMA/HA-DA/GO-βCD-BNN6 was an ideal antibacterial material that improved collagen deposition and angiogenesis and promoted wound healing in a mouse model of full-thickness skin repair, compared to the commercially available Aquacel Ag dressing. We developed a multifunctional nanocomposite hydrogel that exhibited antibacterial and angiogenic properties, adhesiveness, and mechanical properties that enhance the regeneration of bacteria-infected wounds.

In the beginning of the 21st century, therapeutic oligonucleotides have shown great potential for the treatment of many life-threatening diseases. However, effective delivery of therapeutic oligonucleotides to the targeted location in vivo remains a major issue. As an emerging field, DNA nanotechnology is applied in many aspects including bioimaging, biosensing, and drug delivery. With sequence programming and optimization, a series of DNA nanostructures can be precisely engineered with defined size, shape, surface chemistry, and function. Simply with hybridization, therapeutic oligonucleotides including unmethylated cytosine-phosphate-guanine dinucleotide oligos, small interfering RNA (siRNA) or antisense RNA, single guide RNA of the regularly interspaced short palindromic repeat-Cas9 system, and aptamers, are successfully loaded on DNA nanostructures for delivery. In this progress report, the development history of DNA nanotechnology is first introduced, and then the mechanisms and means for cellular uptake of DNA nanostructures are discussed. Next, current approaches to deliver therapeutic oligonucleotides with DNA nanovehicles are summarized. In the end, the challenges and opportunities for DNA nanostructure-based systems for the delivery of therapeutic oligonucleotides are discussed.