Conventional NIR-I photothermal therapy (PTT) has insufficient penetration depth, and the local tissue damage caused by it often concomitants inflammation. Herein, a bifunctional nanoagent based on bovine serum albumin (BSA) and Mo-polyoxometalate (named as B-POM NPs), was developed via a facile self-assembled method for non-inflammatory near-infrared (NIR)-II PTT of triple-negative breast cancer. Thanks for the BSA modification, the obtained B-POM NPs show excellent biocompatibility with high NIR-II photothermal conversion efficiency of 57.2%. In vivo tumor inhibition efficiency under NIR-II PTT reached up to 87 %. More importantly, it is found that the prepared B-POM NPs also have excellent reactive oxygen species scavenging ability. The inflammatory-related factors, such as TNF-α, IL-6 and IL-1β, are significantly down-regulated, which is much beneficial to reduce side effects of PTT. In brief, this work provides a novel protein-based bifunctional nanoagent to effectively inhibit tumor growth meanwhile alleviate inflammatory post NIR-II PTT, showing good promising in clinical.

DNA origami has played an important role in various biomedical applications, including biosensing, bioimaging, and drug delivery. However, the function of the long DNA scaffold involved in DNA origami has yet to be fully exploited. Herein, we report a general strategy for the construction of a genetically encoded DNA origami by employing two complementary DNA strands of a functional gene as the DNA scaffold for gene therapy. In our design, the complementary sense and antisense strands can be directly folded into two DNA origami monomers by their corresponding staple strands. After hybridization, the assembled genetically encoded DNA origami with precisely organized lipids on the surface can function as the template for lipid growth. The lipid-coated and genetically encoded DNA origami can efficiently penetrate the cell membrane for successful gene expression. After decoration with the tumor-targeting group, the antitumor gene (p53) encoded DNA origami can elicit a pronounced upregulation of the p53 protein in tumor cells to achieve efficient tumor therapy. The targeting group-modified, lipid-coated, and genetically encoded DNA origami has mimicked the functions of cell surface ligands, cell membrane, and nucleus for communication, protection, and gene expression, respectively. This rationally developed combination of folding and coating strategies for genetically encoded DNA origami presents a new avenue for the development of gene therapy.

Natural enzymes catalyze biochemical transformations in superior catalytic efficiency and remarkable substrate specificity. The excellent catalytic repertoire of enzymes is attributed to the sophisticated chemical structures of their active sites, as a result of billions-of-years natural evolution. However, large-scale practical applications of natural enzymes are restricted due to their poor stability, difficulty in modification, and high costs of production. One viable solution is to fabricate supramolecular catalysts with enzyme-mimetic active sites. In this review, we introduce the principles and strategies of designing peptide-based artificial enzymes which display catalytic activities similar to those of natural enzymes, such as aldolases, laccases, peroxidases, and hydrolases (mainly the esterases and phosphatases). We also discuss some multifunctional enzyme-mimicking systems which are capable of catalyzing orthogonal or cascade reactions. We highlight the relationship between structures of enzyme-like active sites and the catalytic properties, as well as the significance of these studies from an evolutionary point of view.

DNA nanotechnology has been widely employed in the construction of various functional nanostructures. However, most DNA nanostructures rely on hybridization between multiple single-stranded DNAs. Herein, we report a general strategy for the construction of a double-stranded DNA-ribonucleoprotein (RNP) hybrid nanostructure by folding double-stranded DNA with a covalently bivalent clustered regularly interspaced short palindromic repeats (CRISPR)/nuclease-dead CRISPR-associated protein (dCas) system. In our design, dCas9 and dCas12a can be efficiently fused together through a flexible and stimuli-responsive peptide linker. After activation by guide RNAs, the covalently bivalent dCas9-12a RNPs (staples) can precisely recognize their target sequences in the double-stranded DNA scaffold and pull them together to construct a series of double-stranded DNA-RNP hybrid nanostructures. The genetically encoded hybrid nanostructure can protect genetic information in the folded state, similar to the natural DNA-protein hybrids present in chromosomes, and elicit efficient stimuli-responsive gene transcription in the unfolded form. This rationally developed double-stranded DNA folding and unfolding strategy presents a new avenue for the development of DNA nanotechnology.

Here, we describe a DNA circuit-aided, origami nanodevice-based plasmonic system, which performs DNA-regulated, cascade amplification of faint chemical/biological signals. In this system, two gold-nanorods (GNRs) are co-assembled onto a DNA lock-containing, tweezer-like DNA origami template. Logic circuits serve as recognition and amplification elements for specific messengers, producing DNA keys for driving conformational changes of the plasmonic nanodevices. In the presence of input signals including nucleic acids, adenosines, chiral tyrosinamides or specific receptors expressed by tumor cells, the plasmonic nanodevices can be activated to perform dynamic structural motions, reporting robust responses via plasmonic circular dichroism (CD) spectral changes. This DNA nanodevice-based system provides a different design to enrich the strategies for constructing synthetic nanomachines, enabling the customized bottom-up nanostructure construction for sensitive biological signaling.

Nucleic acid nanostructures are promising biomaterials for the delivery of homologous gene therapy drugs. Herein, we report a facile strategy for the construction of target mRNA (scaffold) and antisense (staple strands) co-assembled RNA/DNA hybrid " origami" for efficient gene therapy. In our design, the mRNA was folded into a chemically well-defined nanostructure through RNA-DNA hybridization with high yield. After the incorporation of an active cell-targeting aptamer, the tailored RNA/DNA hybrid origami demonstrated efficient cellular uptake and controllable release of antisenses in response to intracellular RNase H digestion. The biocompatible RNA/DNA origami (RDO) elicited a noticeable inhibition of cell proliferation based on the silencing of the tumorassociated gene polo-like kinase 1 (PLK1). This RDO-based nanoplatform provides a novel strategy for the further development of gene therapy.

Effective and safe hemodialysis is essential for patients with acute kidney injury and chronic renal failures. However, the development of effective anticoagulant agents with safe antidotes for use during hemodialysis has proven challenging. Here, we describe DNA origami-based assemblies that enable the inhibition of thrombin activity and thrombus formation. Two different thrombin-binding aptamers decorated DNA origami initiates protein recognition and inhibition, exhibiting enhanced anticoagulation in human plasma, fresh whole blood and a murine model. In a dialyzer-containing extracorporeal circuit that mimicked clinical hemodialysis, the origami-based aptamer nanoarray effectively prevented thrombosis formation. Oligonucleotides containing sequences complementary to the thrombin-binding aptamers can efficiently neutralize the anticoagulant effects. The nanoarray is safe and immunologically inert in healthy mice, eliciting no detectable changes in liver and kidney functions or serum cytokine concentration. This DNA origami-based nanoagent represents a promising anticoagulant platform for the hemodialysis treatment of renal diseases.

Natural oxidases mainly rely on cofactors and well-arranged amino acid residues for catalysing electron-transfer reactions but suffer from non-recovery of their activity upon externally induced protein unfolding. However, it remains unknown whether residues at the active site can catalyse similar reactions in the absence of the cofactor. Here, we describe a series of self-assembling, histidine-rich peptides, as short as a dipeptide, with catalytic function similar to that of haem-dependent peroxidases. The histidine residues of the peptide chains form periodic arrays that are able to catalyse H 2 O 2 reduction reactions efficiently through the formation of reactive ternary complex intermediates. The supramolecular catalyst exhibiting the highest activity could be switched between inactive and active states without loss of activity for ten cycles of heating/cooling or acidification/neutralization treatments, demonstrating the reversible assembly/disassembly of the active residues. These findings may aid the design of advanced biomimetic catalytic materials and provide a model for primitive cofactor-free enzymes.

DNA nanostructures have garnered considerable interest as research tools in the field of cell biology and pathology. Herein, we develop an addressable double-bundle DNA tetrahedron with distinct modification sites to load multiple functional components for efficient regulation of gene expression. In our tailored nanoplatform, nucleic acid drugs (antisense for gene therapy) and protein drugs (KillerRed for photodynamic therapy) are precisely organized in the chemically well-defined DNA tetrahedron. With the attachment of active targeting groups, this functional DNA nanocarrier can efficiently penetrate into the cell membrane and subsequently transport drugs to the target subcellular organelles (mitochondrion and nucleus) for inducing synergistic cell behavior regulation to start the endogenous apoptotic process. This tailored DNA nanocarrier provides unprecedented opportunities for intelligent drug delivery and cell biology research.

Using the DNA origami technique, we constructed a DNA nanodevice functionalized with small interfering RNA (siRNA) within its inner cavity and the chemotherapeutic drug doxorubicin (DOX), intercalated in the DNA duplexes. The incorporation of disulfide bonds allows the triggered mechanical opening and release of siRNA in response to intracellular glutathione (GSH) in tumors to knockdown genes key to cancer progression. Combining RNA interference and chemotherapy, the nanodevice induced potent cytotoxicity and tumor growth inhibition, without observable systematic toxicity. Given its autonomous behavior, exceptional designability, potent antitumor activity and marked biocompatibility, this DNA nanodevice represents a promising strategy for precise drug design for cancer therapy.

Nature has evolved enzymes with exquisite active sites that catalyze biotransformations with high efficiency. However, the exploitation of natural enzymes is often hampered by poor stability, and natural enzyme production and purification are costly. Supramolecular self-assembly allows the construction of biomimetic active sites, although it is challenging to produce such artificial enzymes with catalytic activity and stability that rival those of natural enzymes. We report herein a strategy to produce a horseradish peroxidase (HRP) mimic based on the assembly of chitosan with a G-quadruplex DNA (G-DNA)/hemin complex. A network-like morphology of the assembled nanomaterial was observed together with a remarkable enhancement of peroxidase activity induced by the chitosan and G-DNA components. The turnover frequency and catalytic efficiency of the enzyme-mimicking material reached or even surpassed those of HRP. Moreover, the catalytic complex exhibited higher tolerance than HRP to harsh environments, such as extremely low pH or high temperatures. In accord with the experimental and simulated results, it is concluded that the spatial distribution of the G-DNA and chitosan components and the exposure of the catalytic center may facilitate the coordination of substrates by the hemin iron, leading to the superior activity of the material. Our work provides a simple and affordable avenue to produce highly active and robust enzyme-mimicking catalytic nanomaterials.

Enzymes fold into three-dimensional structures to arrange their active groups exquisitely for the remarkable catalytic properties. We are inspired to design and assemble Gln-containing peptides with G-quadruplex DNA/hemin complexes to form the catalytic nanofibrils that possess the horseradish peroxidase-mimicking active sites and catalytic functions. Theoretical simulation results revealed that the intermolecular association of Gln peptide may result in local enrichment and proper orientation of carboxamide groups, which provide potential multivalent hydrogen bonds for enhancing H2O2 affinity to hemin and may behave similarly to distal Arg in a natural heme pocket. The self-folded DNA can provide a guanine base as the axial ligand, and a supramolecular scaffold for supporting and orienting hemin. The beta-sheet forming capability of the Q peptides is found to significantly affect the catalytic synergy between the G-DNA and the peptide. The role of hydrogen bonds network provided by self-assembled Gln peptides is illustrated by solvent kinetic isotope effects and H2O2-induced degradation of hemin. The assembly of the Q peptide with G-DNA/hemin DNAzyme also stimulates the chiroselective oxidization of L-DOPA vs D-DOPA. The incorporation of His-containing peptide into the hemin system via self-assembly, which was demonstrated by confocal colocalization images and fluorescence resonance electron transfer results, further enhanced the catalytic activity of the G-DNA/Q peptide/hemin complex. It is hypothesized that the assembly of the triple components allows mimicking the configuration and the function of the catalytic His-Arg-His triad in horseradish peroxidase. Compared to DNA/hemin or peptide/hemin, the catalytic efficiency of the most active complex shows 10-fold enhanced activity. This work opens an avenue to mimic the catalytic residues and their spatial distribution and may provide a primitive enzyme model for the evolution of modern enzymes. Our results may also have implications for the mechanisms of some cell dysfunctions, which are triggered by catalytic aggregation of biomolecules.

DNA nanostructures are promising biomaterials capable of arranging multiple functional components with nanometer precision. Here, a double-bundle DNA tetrahedron is rationally designed to integrate with antisense oligonucleotides silencing proto-oncogene c-raf and nuclear targeting peptides. The functionalized DNA tetrahedron can be internalized by A549 cells and assists the delivery of antisense oligonucleotides toward the nucleus to increase the chance to downregulate target mRNA in nucleus and cytoplasm. Antisense strands released from the tetrahedron in response to the intracellular reducing environment can inhibit cell proliferation at a low concentration without transfection reagent. Finally, efficient knockdown of c-raf gene is observed, which verified our design. This designer DNA-based nanocarrier system will open a new avenue for efficient delivery of nucleic acid drugs.

The efficient delivery of a therapeutic gene into target tissues has remained a major obstacle in realizing a viable gene-based medicine. Herein, we introduce a facile and universal strategy to construct a DNA nanostructure-based codelivery system containing a linear tumor therapeutic gene (p53) and a chemotherapeutic drug (doxorubicin, DOX) for combined therapy of multidrug resistant tumor (MCF-7R). This novel codelivery system, which is structurally similar to a kite, is rationally designed to contain multiple functional groups for the targeted delivery and controlled release of the therapeutic cargoes. The self-assembled DNA nanokite achieves efficient gene delivery and exhibits effective inhibition of tumor growth in vitro and in vivo without apparent systemic toxicity. These structurally and chemically well-defined codelivery nanovectors provide a new platform for the development of gene therapeutics for not only cancer but also a wide range of diseases.

For over 30 years interventional cardiovascular stenting has been developed from bare metal stents to drugeluting stents and even today's emerging bioabsorbahle stents,continuing to advance the technological therapy for the coronary heart disease.The idea of bioabsorbable stents is to leave no foreign body behind.In general,the stent functions to keep open a blocked artery and maintain the blood flow only until the vessel heals itself,so it would be ideal for the stent to disappear thereafter.Bioresorbable Polymeric Scaffold (BRPS) has gained a great deal of interest in the biomaterials field nowadays because it is made from a polymeric material which can be designed and modified for its intended use,while serving as a good drug carrier.This article discusses the roles of biomaterial,structure and processing in influencing the functions of a BRPS device,with an emphasis on the two manufacturing methods by laser cutting and 3D printing,as well as the degradation kinetics of BRPS.The challenges and trend of BRPS are also discussed.

We herein demonstrate that DNA origami can work as a multifunctional platform integrating a chemotherapeutic drug (doxorubicin), gold nanorods and a tumour-specific aptamer MUC-1, to realize the effective circumvention of drug resistance. Doxorubicin (DOX) was loaded efficiently onto DNA origami through base pair intercalation and surface-modified gold nanorods (AuNRs) were assembled onto the DNA origami through DNA hybridization. Due to the active targeting effect of the assembled aptamers, the multifunctional nanostructures achieved increased cellular internalization of DOX and AuNRs. Upon near-infrared (NIR) laser irradiation, the P-glycoprotein (multidrug resistance pump) expression of multidrug resistant MCF-7 (MCF-7/ADR) cells was down-regulated, achieving the synergistically chemotherapeutic (DOX) and photothermal (AuNRs) effects.

Designing enzyme-mimicking active sites in artificial systems is key to achieving catalytic efficiencies rivaling those of natural enzymes and can provide valuable insight in the understanding of the natural evolution of enzymes. Here, we report the design of a catalytic hemin-containing nanoparticle with self-assembled guanine-rich nucleic acid/histidine-rich peptide components that mimics the active site and peroxidative activity of hemoproteins. The chemical complementarities between the folded nucleic acid and peptide enable the spatial arrangement of essential elements in the active site and effective activation of hemin. As a result, remarkable synergistic effects of nucleic acid and peptide on the catalytic performances were observed. The turnover number of peroxide reached the order of that of natural peroxidase, and the catalytic efficiency is comparable to that of myoglobin. These results have implications in the precise design of supramolecular enzyme mimetics, particularly those with hierarchical active sites. The assemblies we describe here may also resemble an intermediate in the evolution of contemporary enzymes from the catalytic RNA of primitive cells.

Paranemic crossover (PX) DNA motifs were designed and used for self-assembly of two dimensional lattices. The PX motifs tested include overwound and underwound ones, and different forms of selfassembled two-dimensional (2D) lattices were generated, demonstrating the correlation between the helical torsional strain within the system and the quality of the lattice formed. Relief of the torsional strain by adjusting the number of base pairs in the JX region adjacent to the PX motifs, facilitates and optimizes DNA self-assembly, which leads to 2D lattices of greater uniformity and higher yield. This study demonstrated that the helical relationship among DNA building blocks is a critical factor for the tile-based self-assembly of large nanostructures.

In response to environmental variations, living cells need to arrange the conformational changes of macromolecules to achieve the specific biofunctions. Inspired by natural molecular machines, artificial macromolecular assemblies with controllable nanostructures and environmentally responsive functions can be designed. By assembling macromolecular nanostructures with noble metal nanoparticles, environmental information could be significantly amplified and modulated. However, manufacturing dynamic plasmonic nanostructures that are efficiently responsive to different stimuli is still a challenging task. Here we demonstrate a stimulus-responsive plasmonic nanosystem based on DNA origami-organized gold nanorods (GNRs). L-shaped GNR dimers were assembled on rhombus-shaped DNA origami templates. The geometry and chiral signals of the GNR nanoarchitectures respond to multiple stimuli, including glutathione reduction, restriction enzyme action, pH change, or photoirradiation. While the glutathione reduction or restriction enzyme caused irreversible changes in the plasmonic circular dichroism (CD) signals, both pH and light irradiation triggered reversible changes in the plasmonic CD. Our system transduces external stimuli into conformational changes and circular dichroism responses in near-infrared (NIR) wavelengths. By this approach, programmable optical reporters for essential biological signals can be fabricated.