We demonstrate a nanotechnology approach for the development of cancer-cell-specific subcellular organelle-targeted drug nanocarriers based on photostable nanodiamonds (ND) functionalized with folic acid and mitochondrial localizing sequence (MLS) peptides. We showed that these multifunctional NDs not only distinguish between cancer cells and normal cells, and transport the loaded drugs across the plasma membrane of cancer cells, but also selectively deliver them to mitochondria and induce significant cytotoxicity and cell death compared with free Dox localized in lysosomes. Importantly, the cellular uptake of Dox was dramatically increased in a resistant model of MCF-7 cells, which contributed to the significant circumvention of P-glycoprotein-mediated drug resistance. Our work provides a novel method of designing nanodiamond-based carriers for targeted delivery and for circumventing drug resistance in doxorubicin-resistant human breast adenocarcinoma cancer cells.

Because of the chemical simplicity of α-l-threose nucleic acid (TNA) and its ability to exchange genetic information between itself and RNA, it has attracted significant interest as the RNA ancestor. We herein explore the biological properties and evaluate the potency of sequence-designed TNA polymers to suppress the gene expression in living environments. We found that sequence-specific TNA macromolecules exhibit strong affinity and specificity toward the complementary RNA targets, are highly biocompatible and nontoxic in a living cell system, and readily enter a number of cell lines without using transfecting agents. Particularly, TNA exhibited much stronger enzymatic resistance toward fetal bovine serum or human serum as compared to traditional antisense oligonucleotides, which means that the intrinsic structure of TNA is thoroughly resistant to biological degradation. Importantly, the efficacy of the TNA molecule with green fluorescent protein (GFP) target sequence (anti-GFP TNAs) as antisense agents was first demonstrated in living cells in which these polymers revealed high antisense activity in terms of the degree of inhibition of GFP gene expression. The GFP gene inhibition studies in HeLa and HEK293 cells characterize sequence-controlled TNA as a functional biomaterial and a valuable alternative to traditional antisense oligonucleotides such as peptide nucleic acids, phosphorodiamidate morpholino oligomers, and locked nucleic acids for a wide range of applications in drug discovery and life science research. Additionally, we also first reported the cost-efficient approach to synthesize the four TNA phosphoramidite monomers using 2-cyanoethyl N, N, N', N'-tetraisopropylphosphoramidite as a key reagent. Furthermore, by increasing the frequency of the deblocking and coupling reactions together with extending their reaction time in each synthesis cycle, sequence-controlled TNAs can be easily synthesized in a quantitative yield and high purity.

Nuclear-targeting therapy is considered to be a promising strategy of disease treatment. So far, developing biocompatible and nucleus-permeable delivery systems remains a great challenge. Here, we report a nuclear-targeted delivery platform based on 30 nm nanodiamonds (NDs) which were coated with dual-function, cationic peptides consisting of the human immounodeficiency virus TAT protein and a nuclear localization signal (NLS) peptide in aqueous media. As compared to uncoated NDs, cationic peptide-functionalized NDs were confirmed as a small, safe, and efficient carrier which not only facilitates the enhanced cellular uptake and delivery of loaded cargos to the nucleus in a number of cell lines but also shows their advantages of low cytotoxicity and high affinity to antisense oligonucleotides. This peptide-based modification strategy does not contribute greatly to the size of the ND which is important in its use in constructing nuclear targeting vehicles. Compared with traditional gene silencing in cytoplasm, our findings suggest that the nuclear localization effect of ANA4625-TAT-NLS-NDs enhances the therapeutic efficacy of antisense oligonucleotide ANA4625 as evidenced by suppression of the targets bcl-2 and bcl-xL pre-mRNA/protein expressions and the induction of cell apoptosis. The studies have also revealed that NDs can be used to mediate sustained release of antisense agents with preserved therapeutic activity as inhibition of target mRNA expression in a time- and dose-dependent manner. This work not only demonstrates the design of a new nanodiamond-based platform for nuclear targeting but also provides significant insights on nuclear-targeting delivery of cell membrane impermeable therapeutic agents for enhanced disease treatment.

In article number 1603135, S.-Y. Zheng and co-workers develop a point of care device integrated with porous silicon nanowire forests for influenza virus capturing based on their sizes only. By dissolving nanowire forests in physiological aqueous environments, subsequently captured viruses could be released without damage for culturing, characterization, and other analysis. The device shows potential for virus discovery, isolation, and functional studies Nanotheranostics In article number 1602580, J. Lin, P. Huang, Y. Xu, Z. Li, and co-workers present a light/pH dual-stimuli responsive nanotheranostic for multimodal imaging such as two-photon luminescence, fluorescence, photoacoustic, photothermal imaging, as well as trimodal synergistic therapy such as photothermal therapy, photodynamic therapy, and chemotherapy. The cover image depicts how this activatable theranostic nanoplatform fights against cancer like "ten thousand arrows shot at once". Upconversion Nanoparticles Innovative strategies to unleash the freedom of the excitation wavelengths of upconversion nanoparticles have recently been developed. In article number 1602843, W. Huang, G. Han, and co-workers comprehensively review recent advances in the design, property tuning, and applications of ≈800 nm excited upconversion nanoparticles. These nanoparticles show superior potential for biosensing, bioimaging, drug delivery, and therapy. Shifting the upconversion excitation wavelength to a biological "sweet spot" at 800 nm offers opportunities for the further development of lanthanide-doped upcon-version nanoparticles. Recent advances in the emerging ≈800 nm excited upconver-sion nanoparticles, ranging from design principles and property tuning, to their current applications and future development, are discussed. reviews Upconversion Nanoparticles An ultrathin, lightweight, and wearable Li-O 2 battery with a novel segmented structure is first fabricated by employing a "break up the whole into parts" strategy. Superior battery performance including low overpotential, high specific capacity, good rate capability, excellent cycle stability, and high gravimetric/ volumetric energy density (294.68 Wh kg −1 / 274.06 Wh L −1) is successfully achieved even under repeatedly various deformation. communications A novel approach is proposed to enhance the thermal rectification ratio, namely, arranging two thermal rectifiers in series. Through theoretical analysis and molecular dynamics simulations on graphene/ phononic crystal structures, the results show that the series thermal rectifiers enhance thermal rectification ratio significantly , compared to a single rectifier. Meanwhile, the results of theoretical prediction match well with simulation results. A Series Circuit of Thermal Rectifiers: An Effective Way to Enhance Rectification Ratio Fullerene-like nickel oxysulfide hollow nanospheres with ≈50 nm are constructed by in situ growth on the surface of nickel foam by taking advantage of solvothermal reaction. The as-prepared composite exhibits exhilaratingly high HER...

We design and synthesize a sequence-defined α-l-threose nucleic acid (TNA) polymer, which is complementary to certain nucleotide sites of target anti-apoptotic proteins, BcL-2 involving in development and progression of tumors. Compared to scramble TNA, anti-BcL-2 TNA significantly suppresses target mRNA and protein expression in cancerous cells and shows antitumor activity in carcinoma xenografts, resulting in suppression of tumor cell growth and induction of tumor cell death. Together with good biocompatibility, very low toxicity, excellent specificity features, and strong binding affinity toward the complementary target RNAs, TNAs become new useful biomaterials and effective alternatives to traditional antisense oligonucleotides including locked nucleic acids, morpholino oligomers, and peptide nucleic acids in antisense therapy. Compared to conventional cancer therapy such as radiotherapy, surgery, and chemotherapy, we anticipate that this TNA-based polymeric system will work effectively in antisense cancer therapy and shortly start to play an important role in practical application.

A protein-derived nanodiamond-based nanoprobe with targeting properties is established for brain tumor imaging.

We develop a versatile recognition system based on 3D triangular-shaped DNA nanotubes by integrating three different aptamer sequences along the three edges. This would allow multiple binding activities to be combined into a single system. The versatility of this nanotube platform can also provide a framework for spatial orientation and positioning of different aptamer-binding ligands in a 'pea-pod' architecture.

We demonstrated as trategy to reversibly extend and contract 3D DNA nanocages based on G-rich DNA strandsa ss caffolds in the presence of K + or chelating agents. The contraction and extension of nanocage would be regulated by formation and deformationo fGquadruplexi nt he presence of K + ions and chelating agents, respectively.C ompared to single telomeric DNA strands, self-assembled 3D DNA nanocages integrated with three HTLs act as horseradish peroxidase mimicking DNAzymesf or colorimetric detectiona nd monitoring of cholesterol with high stability towardn uclease and blood serum degradations. This is the first example of facile construction of 3D DNA nanostructures with contractile, reversible, and catalytic features based on the assembly and disassembly of G-quadruplexes. This work offers an ew platform for manipulation of nanoscale conformational changes and as tep forwardi no btaining stimuli-responsive 3D DNA nanomaterials with versatile reactivity and functionalities.The base sequence of oligonucleotides, which encodes substantialf unctional and structural information, facilitates the rational design of stimuli-responsive materials.[1] Guanine-rich nucleic acids exhibit not only specificb inding capabilities to various targets including metal ions, [2] proteins [3] or small molecules, [4] but also reversible catalytic functions in the form of hemin/G-quadruplexc omplexes. [5][6][7] The catalytically inactive, random-coil structure of guanine-rich DNA reversibly switches into ac atalytically active G-quadruplex by corresponding input, [8] enablingi ts structuralr econfigurationa nd promoting its applicationsi ns ensing, [3,4,9,10] analytical biochemistry, [11] molecular biology, [12] biomedicine [13] and logic gate development.[14] This G-rich, non-Watson-Crick base-paired building block has been increasingly encoded in self-assembled DNA nanostructures to generate stimuli-responsivet wo dimensional DNA networks [15][16][17] and long DNA nanowires.[18] So far,t he use of G-quadruplex-functionalized 3D DNA nanostructures for structuralr econfiguration is highly limited. Not surprisingly,3 D DNA nanostructures capable of molecular switching play an important role because of their potentialapplications in molecular sensing, drug delivery,m iniaturized robotics and dynamic nanomaterials.[19] Different strategies including addition of specific DNA strands, [20,21] small molecules, [22] protons, [23] enzymes [24] or photons [25] have been used to control the 3D movement in terms of shapes and sizes. Inspired by the reversible conformational switching properties of the G-rich nucleic acids under appropriate conditions, the exploration of stimuliresponsive G-quadruplex-containing 3D DNA nanomaterials with increasing patterns of molecular diversity,c omplexity,a nd functions is still ac hallenge.Herein, we report on the reversible conformationalc hange of 3D DNA nanocages that allows switchable turn ON and OFF of their optical signals. The contraction and extension of HT-NC can be regulated by formation...