Manipulating Radiation-Sensitive Z-DNA Conformation for Enhanced Radiotherapy.

DNA double-strand breaks (DSBs) yield highly determines radiotherapy efficacy. However, improving the inherent radiosensitivity of tumor DNA to promote radiation-induced DSBs remains a challenge. Using theoretical and experimental models, the underexplored impact of Z-DNA conformations on radiosensitivity, yielding higher DSBs than other DNA conformations, is discovered. Thereout, a radiosensitization strategy focused on inducing Z-DNA conformation, utilizing CBL@HfO2 nanocapsules loaded with a Z-DNA inducer CBL0137, is proposed. A hollow mesoporous HfO2 (HM-HfO2) acts as a delivery and an energy depositor to promote Z-DNA breakage. The nanocapsule permits the smart DSBs accelerator that triggers its radiosensitization with irradiation stimulation. Impressively, the CBL@HfO2 facilitates the B-Z DNA conformational transition, augmenting DSBs about threefold stronger than irradiation alone, generating significant tumor suppression with a 30% cure rate. The approach enables DSBs augmentation by improving the inherent radiosensitivity of DNA. As such, it opens up an era of Z-DNA conformation manipulation in radiotherapy.

In Situ Growth 3D GDY-NCNTs Nanocomposites for High-Performance Supercapacitors.

New binary carbon composites (GDY-NCNTs and GDY-CNTs) with a three-dimensional porous structure, which are synthesized by an in situ growth method, are adopted in this article. The GDY-NCNTs composites exhibit excellent specific capacitance performance (679 F g-1, 2 mV s-1, 139% increase compared to GDY-CNTs) and good cycling stability (with a capacity retention rate of up to 116% after 10000 cycles). The three-dimensional porous structure not only promotes ion transfer and increases the effective specific surface area to improve its specific capacitance performance but also adapts to the volume expansion and contraction during the charging and discharging process to improve its cycling stability. The presence of nitrogen doping in the carbon nanotubes of GDY-NCNTs increases the surface defects of the composites, provides more electrochemical points, and improves the surface wettability of the composites, further improving the electrochemical performance of the composites.

Tuning Hole Transport Properties and Perovskite Crystallization via Pyridine-Based Molecules for Quasi-2D Perovskite Solar Cells.

Quasi-2D perovskites show great potential as photovoltaic devices with superior stability, but the power conversion efficiency (PCE) is limited by poor carrier transport. Here, it is simultaneously affected the hole transport layer (HTL) and the perovskite layer by incorporating pyridine-based materials into poly(3,4-ethylenedioxythiophene): polystyrene sulfonate (PEDOT:PSS) to address the key problem above in 2D perovskites. With this approach, the enhanced optoelectronic performance of the novel PEDOT:PSS is due to electron transfer between the additives and PEDOT or PSS, as well as a dissociation between PEDOT and PSS based on experimental and theoretical studies, which facilitates the charge extraction and transfer. Concurrently, in-situ X-ray scattering studies reveal that the introduction of pyridine-based molecules alters the transformation process of the perovskite intermediate phase, which leads to a preferred orientation and ordered distribution caused by the Pb─N chemical bridge, achieving efficient charge transport. As a result, the pyridine-treated devices achieve an increased short-circuit current density (Jsc ) and PCE of over 17%.

In Situ Formed Z-Scheme Graphdiyne Heterojunction Realizes NIR-Photocatalytic Oxygen Evolution and Selective Radiosensitization for Hypoxic Tumors.

Photon radiotherapy is a common tool in the armory against tumors, but it is limited by hypoxia-related radioresistance of tumors and radiotoxicity to normal tissues. Here, we constructed a spatiotemporally controlled synergistic therapy platform based on the heterostructured CuO@Graphdiyne (CuO@GDY) nanocatalyst for simultaneously addressing the two key problems above in radiotherapy. First, the in situ formed Z-scheme CuO@GDY heterojunction performs highly efficient and controlled photocatalytic O2 evolution upon near-infrared (NIR) laser stimulation for tumor hypoxia alleviation. Subsequently, the CuO@GDY nanocatalyst with X-ray-stimulated Cu+ active sites can accelerate Fenton-like catalysis of ·OH production by responding to endogenous H2O2 for the selective killing of tumor cells rather than normal cells. In this way, the sequential combination of NIR-triggered photocatalytic O2 production and X-ray-accelerated Fenton-like reaction can lead to a comprehensive radiosensitization. Overall, this synergism underscores a controllable and precise therapy modality for simultaneously unlocking the hypoxia and non-selectivity in radiotherapy.

Graphdiyne Oxide Quantum Dots: The Enhancement of Peroxidase-like Activity and Their Applications in Sensing H2O2 and Cysteine.

As one of the typical carbon nanomaterials, graphdiyne (GDY) with unique chemical, physical, and electronic properties has a great potential in various fields. Although it is an important member of carbon nanozymes, the research on its intrinsic enzyme mimetic properties and applications is still limited. Herein, graphdiyne oxide quantum dots (GDYO QDs) have been synthesized through oxidative cleavage, which exhibit enhanced peroxidase-like activity with lower Km and higher Vmax than those of most carbon-based nanozymes. The catalytic mechanism is explored, showing that the enhanced catalytic performance is attributed to the good conjugated structure, large number of oxygen-containing groups, and small-sized nanosheets with few layers. As a kind of peroxidase mimetic, the GDY-based nanozyme has excellent potential in sensing H2O2 and biological antioxidants through the colorimetric assay, with a linear range from 5 to 500 µM and detection limit of 1.5 µM for H2O2 and a linear range from 0 to 90 µM and detection limit of 0.48 µM for l-cysteine. Our work will be beneficial to develop high-performance artificial enzymes and to understand their mechanism for better applications.

Transparent graphene electrodes based hybrid perovskites photodetectors with broad spectral response from UV-visible to near-infrared.

A new class of transparent graphene electrode based organic-inorganic halide perovskite photodetectors with broad spectral response is developed. These ultrasensitive devices exhibit high ON/OFF current ratio, high linear dynamic range, broad spectral range, excellent detection for weak light and easy fabrication with low-cost. Their semi-transparent feature and distinct photodetecting function for both sides would provide new applications affecting our daily lives.

High performance determination of Pb2+ in water by 2,4-dithiobiuret-Reduced graphene oxide composite with wide linear range and low detection limit.

In this work, a novel chelating adsorbent, 2, 4-dithiobiuret-reduced graphene oxide composite (DTB-RGO), was synthesized and worked as an electrochemical sensor for the determination of Pb2+. X-ray photoemission spectroscopy, Raman spectroscopy and Fourier transform-infrared spectroscopy were used to confirm the successful doping of the aminothiourea groups into the GO nanosheets through amide bond. The electrode modified with DTB-RGO shows two wide linear range 0.1-200 ng mL-1, 200-1000 ng mL-1 and relatively low detection limit 0.08 ng mL-1 for Pb2+, far below the level of 10 ng mL-1 proposed by WHO. This DTB-RGO modified electrode also presents satisfying selectivity, reproducibility, stability, and applicability for detection of Pb2+, providing a simple and promising platform to develop novel electrochemical sensor for detecting Pb2+ with higher performance.

Amination of the Gd@C82 endohedral fullerene: tunable substitution effect on quantum coherence behaviors.

The core-shell structure of endohedral fullerene-based anisotropic magnetic molecules of high spin with long coherence time could help scale up quantum systems. In this research, by amination of Gd@C82 with morpholine, three derivatives are functionalized with 5, 7 and 9 morpholine groups providing an interesting model to investigate the relationship between the quantum coherence and the spin environment. The original radical located on the carbon cage is successfully quenched, affording a quantum phase memory times (T M) over 5 µs at 5 K. By increasing the number of substitution groups, spin-lattice relaxation times (T 1) also show significant enhancement due to the interaction variation between the molecules and the environments. We found that the T M of the three molecules show no obvious difference below 10 K, while they are limited by T 1 at higher temperatures. In this work, the variable functional groups are able to tune both T 1 and T M, offering the possibility for application of high-spin magnetic molecules in the field of quantum information processing.

Preparing dangling bonds by nanoholes on graphene oxide nanosheets and their enhanced magnetism.

The effects of dangling bonds on the magnetic properties of graphene oxide (GO) were studied experimentally by creating nanoholes on GO nanosheets. GO with more nanoholes (MHGO) and less nanoholes (LHGO) on graphene oxide nanosheets were synthesized. Results showed that nanoholes brought new dangling bonds for GO and the increase of the dangling bonds on GO could be adjusted by the amounts of the nanoholes on GO. The magnetism of GO was enhanced with increased density of nanoholes on GO (MHGO > LHGO > GO). Furthermore, the increased dangling bonds induced magnetic coupling between the spin units and so converted paramagnetism GO to ferromagnetism (MHGO, LHGO). The easy generation and adjustment of GO dangling bonds by nanoholes on GO nanosheets will promote the applications of GO.

Turning On the Near-Infrared Photoluminescence of Erbium Metallofullerenes by Covalent Modification.

The photoluminescence of lanthanide ions inside fullerenes is usually very weak due to the quenching effect of the fullerene cage. In the case of Er@C82, the near-infrared emission from the Er3+ ion is completely quenched by the C82 fullerene cage. It remains challenging to turn on the photoluminescence of Er@C82 and other monometallofullerenes. In this work, we adopt a covalent modification strategy to alter the electronic structure of the fullerene cage for sensitizing the near-infrared emission of Er3+ ions in metallofullerenes Er@C2n (2n = 72, 76, and 82). After covalent modification with trifluoromethyl, phenyl, or dichlorophenyl groups, the erbium metallofullerenes exhibit photoluminescence at 1.5 µm, which is the characteristic emission of the Er3+ ion. Particularly, the otherwise nonfluorescent metallofullerene Er@C82 is transformed into fluorescent derivatives by using this strategy. The photoluminescence from the Er3+ ion is ascribed to energy transfer from the fullerene cage to the Er3+ ion. According to theoretical calculations, the sensitization of the Er3+ ion by the fullerene cage is associated with the large HOMO-LUMO gap and the closed-shell electronic structure of the metallofullerene derivatives. This work provides useful guidance for the design and synthesis of new fluorescent metallofullerenes.

The Gold Nanocluster Protects Neurons Directly or via Inhibiting Cytotoxic Secretions of Microglia Cell.

Neurodegenerative diseases have become a huge challenge to public health, such as Alzheimer's and Parkinson's diseases. Microglia driving inflammation in the central nervous system (CNS) has been involved in the pathological process of these disorders and could be novel therapy target. However, traditional anti-inflammatory drugs are not effective in alleviating neuroinflammation. In this study, a potential neuroprotective effect of a peptide-templated gold nanocluster (Au25Sv9) was investigated. Firstly, effect of the nanocluster on cytotoxins' secretion of activated BV-2 microglia cells was assessed. Results indicated Au25Sv9 nanocluster effectively attenuated the cytotoxicity of stimulated microglia cells towards neuronal cells. And the underlying mechanism of action was illuminated preliminarily. The secretions of IL-6, TNF-α and NO in activated microglia cells were inhibited by the nanocluster in a dose-dependent manner via suppressing the activation of NF-κB and p38 pathways. Moreover, the ability of the nanocluster to protect neuronal cells to against microglial cytotoxins was also evaluated. Treating neuronal cells with the nanoclusters could protect them from cytotoxicity induced by supernatants of stimulated microglia cells through up-regulating of hemeoxygenase-1 (HOX-1). This study suggested the peptide-templated gold nanocluster is able to reduce microglia-mediated cytotoxicity to neuronal cells and possess direct neuroprotective properties simultaneously. We deduce the gold nanocluster would be an effective therapeutic approach to against neuroinflammation driving neurodegenerative diseases in the future.

A Flexible Hot-Film Sensor Array for Underwater Shear Stress and Transition Measurement.

A flexible hot-film sensor array for wall shear stress, flow separation, and transition measurement has been fabricated and implemented in experiments. Parylene C waterproof layer is vapor phase deposited to encapsulate the sensor. Experimental studies of shear stress and flow transition on a flat plate have been undertaken in a water tunnel with the sensor array. Compared with the shear stress derived from velocity profile and empirical formulas, the measuring errors of the hot-film sensors are less than 5%. In addition, boundary layer transition of the flat plate has also been detected successfully. Ensemble-averaged mean, normalized root mean square, and power spectra of the sensor output voltage indicate that the Reynolds number when transition begins at where the sensor array located is 1.82 × 105, 50% intermittency transition is 2.52 × 105, and transition finishes is 3.96 × 105. These results have a good agreement with the transition Reynolds numbers, as measured by the Laser Doppler Velocimetry (LDV) system.

Nanoparticles with High-Surface Negative-Charge Density Disturb the Metabolism of Low-Density Lipoprotein in Cells.

Endocytosis is an important pathway to regulate the metabolism of low-density lipoprotein (LDL) in cells. At the same time, engineering nanoparticles (ENPs) enter the cell through endocytosis in biomedical applications. Therefore, a crucial question is whether the nanoparticles involved in endocytosis could impact the natural metabolism of LDL in cells. In this study, we fabricated a series of gold nanoparticles (AuNPs) (13.00 ± 0.69 nm) with varied surface charge densities. The internalized AuNPs with high-surface negative-charge densities (HSNCD) significantly reduced LDL uptake in HepG-2, HeLa, and SMMC-7721 cells compared with those cells in control group. Notably, the significant reduction of LDL uptake in cells correlates with the reduction of LDL receptors (LDL-R) on the cell surface, but there is no change in protein and mRNA of LDL-Rs. The cyclic utilization of LDL-R in cells is a crucial pathway to maintain the homoeostasis of LDL uptake. The release of LDL-Rs from LDL/LDL-R complexes in endosomes depended on reduction of the pH in the lumen. AuNPs with HSNCD hampered vacuolar-type H⁺-ATPase V1 (ATPaseV1) and ATPaseV0 binding on the endosome membrane, blocking protons to enter the endosome by the pump. Hence, fewer freed LDL-Rs were transported into recycling endosomes (REs) to be returned to cell surface for reuse, reducing the LDL uptake of cells by receptor-mediated endocytosis. The restrained LDL-Rs in the LDL/LDL-R complex were degraded in lysosomes.

Fluorescent activatable gadofullerene nanoprobes as NIR-MR dual-modal in vivo imaging contrast agent.

Dual mode imaging technology is widely developed to achieve the early-stage precision cancer diagnosis. Here we designed a dual-modal magnetic resonance/near infrared fluorescence optical imaging contrast agent (GdF-SS-NIR783) with the fluorescence activatable and safer gadofullerene. The nanoprobes were fabricated by conjugating the gadofullerene derivatives with a NIR fluorescence imaging agent (NIR783) via the disulfide bond. The obtained nanoprobes showed no fluorescence (OFF), but the fluorescence turned on when incubated within reduction environment such as GSH solution. The clear fluorescence signal in tumor site was observed obviously after their intratumor injection. The nanoprobes also revealed efficient MRI contrast enhancement both in vitro and in vivo. And they showed good biocompatibility and did not demonstrate any tissue toxicity in vivo. This work gave the new possibility in designing more efficient and safer nanoprobes for future medical diagnoses.

Gd@C82(OH)22 harnesses inflammatory regeneration for osteogenesis of mesenchymal stem cells through JNK/STAT3 signaling pathway.

Tissue injuries are inevitably accompanied with immune responses. Understanding the effects of biomaterials on immunology regulation is critical for biomaterial development and tissue regeneration. Inflammatory cytokines secreted from macrophages promote the migration of mesenchymal stem cells (MSCs) to the damaged tissue sites and their subsequent participation in tissue repair. However, the effects of inflammatory cytokines caused by tissue injury on MSC behaviors urgently need to be revealed. Understanding and subsequently manipulating the interactions between immune cells and stem cells will provide us with new therapeutic strategies for tissue regeneration. Nanoparticles having immunomodulatory properties can modulate MSCs' functions in the inflammatory microenvironment. In this study, an immunomodulatory nanoparticle Gd@C82(OH)22 was used to manipulate MSC differentiation in inflammatory microenvironment. The results suggested that macrophage-derived inflammation induces osteogenic differentiation of MSCs by activating the JNK/STAT3 pathway. Gd@C82(OH)22 modulates inflammation-induced differentiation of MSCs in a dose-dependent manner through the JNK/STAT3 pathway. Low concentration of Gd@C82(OH)22 facilitates osteogenesis and high concentration suppresses osteogenesis of hMSCs in the inflammatory microenvironment. This study suggests that Gd@C82(OH)22 can act as a promising immunomodulator to differentiate stem cells and improve stem cell-based therapeutic efficiency for biomedical regeneration in inflammatory microenvironments.

Study on the antigenicity of metallofullerenol: antibody production, characterization, and its enzyme immunoassay application.

With their intriguing structures and properties, metallofullerenols have attracted considerable attention in biological and medical applications. Due to the increasing biomedical interest, effective detection methods are important to monitor and control metallofullerenols. However, the detection of metallofullerenols becomes very difficult after polyhydroxylated modification due to the lack of detectable features. Antibody-based immunoassay methods have been important tools for detection and will better meet the needs of analysis of metallofullerenols. Thus, the antigenicity of metallofullerenol has been studied for the first time. In this study, no immune response was detected when metallofullerenol Gd@C82(OH)x was used as immunogen. However, the polyclonal antibody against metallofullerenol was produced using metallofullerenol-KLH (keyhole limpet hemocyanin) as immunogen, indicating that metallofullerenol can act as hapten. The specificity of the obtained antibody was investigated. It has been found that the hydroxyl groups on the surface of the carbon cage, the encapsulated metal, and the size and shape of the carbon cage did not affect the recognition specificity of the antibody. Based on the obtained antibody, an indirect competitive enzyme immunoassay was developed for the determination of metallofullerenol with detection limits of 18 ng/mL in PBS. This enzyme immunoassay method was successfully used to detect metallofullerenol in serum. This work can provide an innovative way to determine metallofullerenols. Graphical abstract The polyclonal antibody against metallofullerenol was produced using metallofullerenol-KLH (keyhole limpet hemocyanin) as immunogen. Based on the obtained antibody, a competitive enzyme immunoassay was developed for the determination of metallofullerenol.

Metallofullerenol Inhibits Cellular Iron Uptake by Inducing Transferrin Tetramerization.

Herein, A549 tumor cell proliferation was confirmed to be positively dependent on the concentration of Fe3+ or transferrin (Tf). Gd@C82 (OH)22 or C60 (OH)22 effectively inhibited the iron uptake and the subsequent proliferation of A549 cells. The conformational changes of Tf mixed with FeCl3 , GdCl3 , C60 (OH)22 or Gd@C82 (OH)22 were obtained by SAXS. The results demonstrate that Tf homodimers can be decomposed into monomers in the presence of FeCl3 , GdCl3 or C60 (OH)22 , but associated into tetramers in the presence of Gd@C82 (OH)22 . The larger change of SAXS shapes between Tf+C60 (OH)22 and Tf+FeCl3 implies that C60 (OH)22 is bound to Tf, blocking the iron-binding site. The larger deviation of the SAXS shape from a possible crystal structure of Tf tetramer implies that Gd@C82 (OH)22 is bound to the Tf tetramer, thus disturbing iron transport. This study well explains the inhibition mechanism of Gd@C82 (OH)22 and C60 (OH)22 on the iron uptake and the proliferation of A549 tumor cells and highlights the specific interactions of a nanomedicine with the target biomolecules in cancer therapy.

Polyhydroxylated fullerenols regulate macrophage for cancer adoptive immunotherapy and greatly inhibit the tumor metastasis.

Adoptive immunotherapy is a highly effective approach for cancer treatment. Several potential adoptive immunotherapies have high (though reversible) toxicities with disappointing results. Polyhydroxylated fullerenols have been demonstrated as promising antitumor drugs with low toxicities. In this study, we investigate whether polyhydroxylated fullerenols (C60(OH)22 and Gd@C82(OH)22) contribute to cancer immunotherapy by regulating macrophages. Our results show that fullerenols treatment enhances mitochondrial metabolism, phagocytosis and cytokine secretion. Moreover, activated macrophages inhibit the growth of several cancer cell types. It is likely that this inhibition is dependent on an NF-κB-mediated release of multiple cytokines. Using a lung metastasis model, we also show that autologous macrophages greatly suppress cancer cell metastasis to lung when they are activated by C60(OH)22 and Gd@C82(OH)22. More importantly, Gd@C82(OH)22 are shown to have stronger ability than C60(OH)22 to improve the macrophage function, which shed light on the rational design for nanomedicine and clinical application. FROM THE CLINICAL EDITOR: The interest in the use of immunotherapy in cancer has rekindled recently. However, many approaches have shown disappointing results. In this study, the authors investigated the effects of polyhydroxylated fullerenol nanoparticles on regulating macrophages for immunotherapy. These positive findings may point a novel way to cancer treatment.

Isomers of IC70BA and Their Photovoltaic Performance in Polymer Solar Cells.

Indene-C70 derivatives were synthesized, including indene-C70 mono-adduct (IC70MA), indene-C70 bis-adduct (IC70BA) and indene-C70 tris-adduct (IC70TA). All as-prepared fullerene adducts are in fact a mixture of isomers. The IC70BA mixture was further separated by high-performance liquid chromatography (HPLC) and two different IC70BA isomers were obtained. With the addition of the increased number of indene, the lowest unoccupied molecular orbital (LUMO) energy level of the C70 derivatives is also increased. IC70BA and its isomers have a slight difference in LUMO energy level, but show great differences in the absorption spectra. Polymer solar cells (PSCs) devices were fabricated under the same conditions with P3HT as donor, IC70BA and its isomer as acceptor, to examine the influence of the regioisomers on photovoltaic performance. The two IC70BA isomers exhibited varying power conversion efficiency (PCE) values of 2.80 and 3.18%, respectively, suggesting the molecular structure of the fullerene derivatives have an effect on polymer solar cells properties.

Divalent metals can reside on bonds in fullerenes.

DFT calculations consistently suggest that a lanthanide will sit on either the 6/6 bond inside C60 having a divalent state or the hexagonal center having a trivalent state. Some lanthanides can stay only above the 6/6 bond inside C60 to form stabilized structures, despite the greatly reduced metal-cage coordination numbers. The preference for C-C bonds by a divalent metal has been confirmed by revisiting the structures of Yb@C2v(3)-C80, Yb@Cs(6)-C82 and Yb@C2v(9)-C82, for which the calculations suggest that the Yb atoms are indeed situated above the C-C bonds, close to the reported structures obtained by single crystal XRD experiments. The result will guide the characterization of structures and electronic structures of endohedral metallofullerenes (EMFs), especially C60 mono-EMFs, in the future.