Intracellular accumulation of reactive oxygen species (ROS) leads to oxidative stress, which is closely associated with many diseases. Introducing artificial organelles to ROS-imbalanced cells is a promising solution, but this route requires nanoscale particles for efficient cell uptake and micro-scale particles for long-term cell retention, which meets a dilemma. Herein, we report a deoxyribonucleic acid (DNA)-ceria nanocomplex-based dynamic assembly system to realize the intracellular in-situ construction of artificial peroxisomes (AP). The DNA-ceria nanocomplex is synthesized from branched DNA with i-motif structure that responds to the acidic lysosomal environment, triggering transformation from the nanoscale into bulk-scale AP. The initial nanoscale of the nanocomplex facilitates cellular uptake, and the bulk-scale of AP supports cellular retention. AP exhibits enzyme-like catalysis activities, serving as ROS eliminator, scavenging ROS by decomposing H2O2 into O2 and H2O. In living cells, AP efficiently regulates intracellular ROS level and resists GSH consumption, preventing cells from redox dyshomeostasis. With the protection of AP, cytoskeleton integrity, mitochondrial membrane potential, calcium concentration and ATPase activity are maintained under oxidative stress, and thus the energy of cell migration is preserved. As a result, AP inhibits cell apoptosis, reducing cell mortality through ROS elimination.

Conspectus Developing a new system of material chemistry is an important molecular foundation for the design and preparation of functional materials, which resembles the preparation of raw materials such as bricks for constructing a building that determines the quality of the building. However, precisely controlling the synthesis processes and structures of functional materials always remains a grand challenge. It is expected to propose a paradigm of “gene-like” precise construction to realize the rational synthesis of functional materials, i.e., a “structure-function-application” principle for the precise construction. As the core genetic material of life, the DNA molecule is a bioactive macromolecule that can accurately encode genetic information and also can act as the generic molecular building block for the precise construction of functional materials. In this Account, we describe our work on the design and construction of functional DNA materials, to illustrate the principle of “gene-like” construction of functional DNA materials. The DNA molecule shows the unique advantages in the “gene-like” construction of functional materials, mainly including the precise arrangement of bases (monomers), the controllable design and assembly of structure, the precise transmission of sequence information, and customization of function. First, the number and sequence of four deoxynucleotide monomers that constitute the DNA strand can be rationally designed and accurately synthesized. Second, the sequence information on DNA endows the precise and efficient assembly of DNA molecules and ensures the precise regulation on the specific biological functions of functional DNA materials. Third, the functions of DNA materials can couple with the biological environments, so as to achieve the predetermined applications. Based on the scale of the constructed DNA materials, we categorize DNA materials into three classes: molecular scale, nanoscale, and macroscale. At the molecular scale, the representative material is branched DNA-based materials; the construction strategies mainly include target-triggered polymerization, enzymatic extension, and hybrid coupling; the applications mainly include the nonenzymatic detection of base mutation, the construction of artificial cells for the study of compartmentalization and the confinement effect, and the regulation of optical and antibacterial properties of supernanoclusters. At the nanoscale, the representative material is the DNA nanocomplex; the construction strategies mainly include hybridization with polymer, small molecule, and metal ions; the applications mainly include gene drug delivery and luminescence bioimaging. At the macroscale, the representative material is the DNA hydrogel; the construction strategies mainly include double-rolling circle amplification (double-RCA), multistage-RCA, and chemical cross-linking; the applications mainly include cell isolation, cell delivery, antibacterial agents, and self-healing electric circuits. Based on the “gene-like” paradigm, we expect to d...

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Branched DNA with multibranch-like anisotropic topology serves as a promising and powerful building block in constructing multifunctional-integrated nanomaterials in a programmable and controllable manner. Recently, a series of branched DNA-based functional nanomaterials were developed by elaborate molecular design. In this review, we focused on the construction of branched DNA-based nanostructures for biological and biomedical applications. First, the molecular design and synthesis method of branched DNA monomer were briefly described. Then, the construction strategies of branched DNA-based nanostructures were categorially discussed, including target-triggered polymerization, enzymatic extension and hybrid assembly. Finally, the biological and biomedical applications including diagnosis, therapeutics and protein engineering were summarized. We envision that the review will contribute to the further development of branched DNA-based nanomaterials with great application potential in the field of biomedicine, thus building a new bridge between material chemistry and biomedicine.