Cell entry of anionic nano-objects has been observed in various types of viruses and self-assembled DNA nanostructures. Nevertheless, the physical mechanism underlying the internalization of these anionic particles across the negatively charged cell membrane remains poorly understood. Here, we report the use of virus-mimicking designer DNA nanostructures with near-atomic resolution to program “like-charge attraction” at the interface of cytoplasmic membranes. Single-particle tracking shows that cellular internalization of tetrahedral DNA nanostructures (TDNs) depends primarily on the lipid-raft-mediated pathway, where caveolin plays a key role in providing the short-range attraction at the membrane interface. Both simulation and experimental data establish that TDNs approach the membrane primarily with their corners to minimize electrostatic repulsion, and that they induce uneven charge redistribution in the membrane under the short-distance confinement by caveolin. We expect that the nanoscale like-charge attraction mechanism provides new clues for viral entry and general rules for rational design of anionic carriers for therapeutics.

Cells existing in the form of clusters often exhibit distinct physiological functions from their monodispersed forms, which have a close association with tissue and organ development, immunoresponses, and cancer metastasis. Nevertheless, the ability to construct artificial cell clusters as in vitro models for probing and manipulating intercellular communications remains limited. Here we design DNA origami nanostructure (DON)-based biomimetic membrane channels to organize cell origami clusters (COCs) with controlled geometric configuration and cell–cell communications. We demonstrate that programmable patterning of homotypic and heterotypic COCs with different configurations can result in three distinct types of intercellular communications: gap junctions, tunneling nanotubes, and immune/tumor cell interactions. In particular, the organization of T cells and cancer cells with a prescribed ratio and geometry can program in vitro immunoresponses, providing a new route to understanding and engineering cancer immunotherapy.

In the last few years the GaN‐based white light‐emitting diode (LED) has been remarkable as a commercially available solid‐state light source. To increase the luminescence power, we studied GaN LED epitaxial materials. First, a special maskless V‐grooved c‐plane sapphire was fabricated, a GaN lateral epitaxial overgrowth method on this substrate was developed, and consequently GaN films are obtained with low dislocation densities and an increased light‐emitting efficiency (because of the enhanced reflection from the V‐grooved plane). Furthermore, anomalous tunneling‐assisted carrier transfer in an asymmetrically coupled InGaN/GaN quantum well structure was studied. A new quantum well structure using this effect is designed to enhance the luminescent efficiency of the LED to ∼72%. Finally, a single‐chip phosphor‐free white LED is fabricated, a stable white light is emitted for currents from 20 to 60 mA, which makes the LED chip suitable for lighting applications.

No abstract

The capacity of natural killer (NK) cells to kill tumor cells without specific antigen recognition provides an advantage over T cells and makes them potential effectors for tumor immunotherapy. However, the efficacy of NK cell adoptive therapy can be limited by the immunosuppressive tumor microenvironment. Transforming growth factor-β (TGF-β) is a potent immunosuppressive cytokine that can suppress NK cell function. To convert the suppressive signal induced by TGF-β to an activating signal, we genetically modified NK-92 cells to express a chimeric receptor with TGF-β type II receptor extracellular and transmembrane domains and the intracellular domain of NK cell-activating receptor NKG2D (TN chimeric receptor). NK-92 cells expressing TN receptors were resistant to TGF-β-induced suppressive signaling and did not down-regulate NKG2D. These modified NK-92 cells had higher killing capacity and interferon γ (IFN-γ) production against tumor cells compared with the control cells and their cytotoxicity could be further enhanced by TGF-β. More interestingly, the NK-92 cells expressing TN receptors were better chemo-attracted to the tumor cells expressing TGF-β. The presence of these modified NK-92 cells significantly inhibited the differentiation of human naïve CD4 T cells to regulatory T cells. NK-92-TN cells could also inhibit tumor growth in vivo in a hepatocellular carcinoma xenograft tumor model. Therefore, TN chimeric receptors can be a novel strategy to augment anti-tumor efficacy in NK cell adoptive therapy.

under the context that Brentuximab vedotin (Adcetris) for relapsed Hodgkin lymphoma [5,6] and T-DM1 (Kadcyla) for HER2 + metastatic breast cancer [7,8] received clinical approval from the Food and Drug Administration (FDA). The socalled "magic bullet," originally conceived by Paul Ehrlich, [9] are designed to combine the toxicity of small-molecule drugs with the targeting ability of antibodies to improve overall efficacy and therapeutic index. [10][11][12][13][14][15] Although conceptually straightforward, development of ADCs is encountered with several challenges including manageable toxicity, homogeneous conjugation and limited drug payload capacity. The balance between drug-to-antibody ratio (DAR) and targeting capability is mandatory for ADCs to reduce the attrition rate of drug candidates. Very high DAR ADCs may suffer decreased recognition to the target antigen. [16][17][18][19] Hence, it is highly desirable to develop ADCs with both high maximum tolerated doses and high selectivity. [20][21][22] Recently, the bloom of structural DNA nanotechnology [23,24] has demonstrated unprecedented precision on structural control, which enables predictable and programmable construction of complex nanostructures by exploiting intra-and inter-molecular Watson-Crick base-pairing. The programmability and addressability of DNA origami nanostructures (DONs) enable multiple desired functional moieties (such as therapeutic cargoes and tumor targeting ligands) with designer geometry and density. [25][26][27] Therefore, DONs have been increasingly employed for developing novel drug delivery systems [28,29] due to their versatile designability, high solubility, and intrinsic biocompatibility. [30][31][32][33][34][35][36][37] Moreover, certain types of DONs have been proven to be readily rapidly internalized by mammalian cells despite their negatively charged surface property. [38] We herein propose that DONs with certain framework [39] could serve as an ideal scaffold for ADCs analogues with exceptional control over targeting ligand density and drug loading contents for optimized antitumor efficacies and safety profile. [40] Specifically, we construct a new prostate cancer (PCa)specific drug delivery system by introducing different numbers of ligand 2-[3-(1,3-dicarboxy propyl)-ureido] pentanedioic acid (DUPA) to a designed six-helical-bundle DNA origami nanostructure (6HB DON). DUPA has been demonstrated to be a high-affinity inhibitor (K i ≈ 0.02 × 10 −9 -0.1 × 10 −9 m) for prostate-specific membrane antigen (PSMA). [41] We incorporate this Effective drug delivery systems that can systematically and selectively transport payloads to disease cells remain a challenge. Here, a targeting ligandmodified DNA origami nanostructure (DON) as an antibody-drug conjugate (ADC)-like carrier for targeted prostate cancer therapy is reported. Specifically, DON of six helical bundles is modified with a ligand 2-[3-(1,3-dicarboxy propyl)-ureido] pentanedioic acid (DUPA) against prostate-specific membrane antigen (PSMA), to serve as the antibody f...

Fluorescent copper nanoclusters (CuNCs) have been widely used in chemical sensors, biological imaging, and lightemitting devices. However, individual fluorescent CuNCs have limitations in their capabilities arising from poor photostability and weak emission intensities. As one kind of aggregationinduced emission luminogen (AIEgen), the formation of aggregates with high compactness and good order can efficiently improve the emission intensity, stability, and tunability of CuNCs. Here, DNA nanoribbons, containing multiple specific binding sites, serve as a template for in situ synthesis and assembly of ultrasmall CuNCs (0.6 nm). These CuNC selfassemblies exhibit enhanced luminescence and excellent fluorescence stability because of tight and ordered arrangement through DNA nanoribbons templating. Furthermore, the stable and bright CuNC assemblies are demonstrated in the high-sensitivity detection and intracellular fluorescence imaging of biothiols. Fluorescent copper nanoclusters (CuNCs) are extensively employed in the areas of chemical sensors, [1] biological imaging, [1c, 2] and light emitting devices [3] because of their large Stokes shift, low toxicity, good biocompatibility, and low cost. To date, various synthetic strategies have been proposed

DNA nanostructures have attracted great attention due to their precisely controllable geometry and great potential in various areas including bottom-up self-assembly. However, construction of higher-order DNA nanoarchitectures with individual DNA nanostructures is often hampered with the purity and quantity of these "bricks". Here, we introduced size exclusion chromatography (SEC) to prepare highly purified tetrahedral DNA nanocages in large scale and demonstrated that precise quantification of DNA nanocages was the key to the formation of higher-order DNA nanoarchitectures. We successfully purified a series of DNA nanocages with different sizes, including seven DNA tetrahedra with different edge lengths (7, 10, 13, 17, 20, 26, 30 bp) and one trigonal bipyramid with a 20-bp edge. These highly purified and aggregation-free DNA nanocages could be self-assembled into higher-order DNA nanoarchitectures with extraordinarily high yields (98% for dimer and 95% for trimer). As a comparison, unpurified DNA nanocages resulted in low yield of 14% for dimer and 12% for trimer, respectively. AFM images cleraly presented the characteristic structure of monomer, dimer and trimer, impling the purified DNA nanocages well-formed the designed nanoarchitectures. Therefore, we have demonstrated that highly purified DNA nanocages are excellent "bricks" for DNA nanotechnology and show great potential in various applications of DNA nanomaterials.