Metal-Organic Framework PCN-224 Combined Cobalt Oxide Nanoparticles for Hypoxia Relief and Synergistic Photodynamic/Chemodynamic Therapy.

Photodynamic therapy (PDT) and chemodynamic therapy (CDT) are promising tumor treatments mediated by reactive oxygen species (ROS), which have the advantages of being minimally invasive. However, the hypoxia of tumor microenvironment and poor target ability often reduce the therapeutic effect. Here we propose a tumor targeted nanoplatform PCN-224@Co3O4-HA for enhanced PDT and synergistic CDT, constructed by hyaluronate-modified Co3O4 nanoparticles decorated metal-organic framework PCN-224. Co3O4 can catalyze the decomposition of highly expressed H2O2 in tumor cells to produce oxygen and alleviate the problem of hypoxia. It can also produce hydroxyl radicals according to the Fenton-like reaction for chemical dynamic therapy, significantly improving the therapeutic effect. The cell survival experiment showed that after in vitro treatment, 4T1 and MCF-7 cancer cells died in a large area under the anaerobic state, while the survival ability of normal cell L02 was nearly unchanged. This result effectively indicated that PCN-224@Co3O4-HA could effectively relieve tumor hypoxia and improve the effect of PDT and synergistic CDT. Cell uptake experiments showed that PCN-224@Co3O4-HA had good targeting properties and could effectively aggregate in tumor cells. In vivo experiments on mice, PCN-224@Co3O4-HA presented reliable biosafety performance, and can cooperate with PDT and CDT therapy to prevent the growth of tumor.

Ultrabright Xanthene Fluorescence Probe for Mitochondrial Super-Resolution Imaging.

Mitochondria are important organelles that provide energy for cellular physiological activities. Changes in their structures may indicate the occurrence of diseases, and the super-resolution imaging of mitochondria is of great significance. However, developing fluorescent probes for mitochondrial super-resolution visualization still remains challenging due to insufficient fluorescence brightness and poor stability. Herein, we rationally synthesized an ultrabright xanthene fluorescence probe Me-hNR for mitochondria-specific super-resolution imaging using structured illumination microscopy (SIM). The rigid structure of Me-hNR provided its ultrahigh fluorescence quantum yield of up to 0.92 and ultrahigh brightness of up to 16,000. Occupying the para-position of the O atom in the xanthene skeleton by utilizing the smallest methyl group ensured its excellent stability. The study of the photophysical process indicated that Me-hNR mainly emitted fluorescence via radiative decay, and nonradiative decay and inter-system crossing were rare due to the slow nonradiative decay rate and large energy gap (ΔEst = 0.55 eV). Owing to these excellent merits, Me-hNR can specifically light up mitochondria at ultralow concentrations down to 5 nM. The unprecedented spatial resolution for mitochondria with an fwhm of 174 nm was also achieved. Therefore, this ultrabright xanthene fluorescence probe has great potential in visualizing the structural changes of mitochondria and revealing the pathogenesis of related diseases using SIM.

CRISPR/Cas systems combined with DNA nanostructures for biomedical applications.

DNA nanostructures are easy to design and construct, have good biocompatibility, and show great potential in biosensing and drug delivery. Numerous distinctive and versatile DNA nanostructures have been developed and explored for biomedical applications. In addition to DNA nanostructures that are completely assembled from DNA, composite DNA nanostructures obtained by combining DNA with other organic or inorganic materials are also widely used in related research. The CRISPR/Cas system has attracted great attention as a powerful gene editing technology and is also widely used in biomedical diagnosis. Many researchers are committed to exploring new possibilities by combining DNA nanostructures with CRISPR/Cas systems. These explorations provide support for the development of new detection methods and cargo delivery pathways, provide inspiration for improving relevant gene editing platforms, and further expand the application scope of DNA nanostructures and CRISPR/Cas systems. This paper mainly reviews the design principles and biomedical applications of CRISPR/Cas combined with DNA nanostructures based on the types of DNA nanostructures. Finally, the application status, challenges and development prospects of CRISPR/Cas combined with DNA nanostructures in detection and delivery are summarized. It is expected that this review will enable researchers to better understand the current state of the field and provide insights into the application of CRISPR/Cas systems and the development of DNA nanostructures.

Immobilization of horseradish peroxidase on metal-organic framework to imporve enzyme activity for enhanced chemodynamic therapy.

Bio-enzymes have the advantages of strong substrate specificity, high catalytic efficiency, and minimal toxic side effects, making them promising drugs in cancer therapy. However, the poor stability and cellular penetrability of uncoated protein in the physiological environment severely restricts the direct application of Bio-enzyme. To address it, we report a metal-organic framework (MOF), Hf-DBA (H2DBA, biphenyl carboxylic acid ligands). The morphology of the Hf-DBA was revealed by TEM and the diameter was in the range of 200 to 350 nm. Hf-DBA acted a carrier for intracellular delivery and protection of horseradish peroxidase (HRP). The prepared HRP@Hf-DBA can catalyze the excess H2O2 in the tumor cells to generation of •OH for chemodynamic therapy (CDT). Compared with free HRP, the catalytic activity of HRP@Hf-DBA is significantly improved, and the optimal catalytic conditions are explored. The catalytic stability of HRP@Hf-DBA remained above 70% after 12 cycles of catalysis. After treatment with HRP@Hf-DBA, the apoptosis rates of A549 and Hela cells was 71.64%, and 76.86%. The results in vitro show that HRP@Hf-DBA can effectively inhibit the growth of tumor cells through enhanced CDT.

Ultra-compact on-chip meta-waveguide phase modulator based on split ring magnetic resonance.

With the development of photonic integration technology, meta-waveguides have become a new research hotspot. They have broken through the theoretical diffraction limit by virtue of the strong electromagnetic manipulation ability of the metasurface and the strong electromagnetic field limitation and guidance ability of the waveguide. However, the reported meta-waveguides lack research on dynamic modulation. Therefore, we analyze the modulation effect of the metasurface on the optical field in the waveguide and design an ultra-compact on-chip meta-waveguide phase modulator using split ring magnetic resonance. It has a very short modulation length of only 3.65 µm, wide modulation bandwidth of 116.8 GHz, and low energy consumption of 263.49 fJ/bit. By optimizing the structure, the energy consumption can be further reduced to 90.69 fJ/bit. Meta-waveguides provide a promising method for the design of integrated photonic devices.

Adjustable strong circular dichroism based on a tricircular arc metasurface.

Circular dichroism has promising applications in biology, molecular chemistry, and other fields. The key to obtaining strong circular dichroism is to introduce symmetry breaking into the structure, which leads to a great difference in the response to different circularly polarized waves. Here, we propose a metasurface structure based on three circular arcs, which produces strong circular dichroism. The metasurface structure combines the split ring with the three circular arcs and increases the structural asymmetry by changing the relative torsional angle. The causes of the strong circular dichroism are analyzed in this paper, and the influence of metasurface parameters on it is discussed. According to the simulation data, the response of the proposed metasurface to different circularly polarized waves varies greatly, with absorption of up to 0.99 at 5.095 THz for a left-handed circularly polarized wave and a maximum circular dichroism of over 0.93. In addition, the incorporation of the phase change material vanadium dioxide on the structure allows flexible modulation of circular dichroism and modulation depths of up to 98.6%. The change of angle within a certain range has little effect on the structural performance. We believe that this flexible and angle robust chiral metasurface structure is suitable for complex reality, and large modulation depth is more practical.

TLR2 mediates autophagy through ERK signaling pathway in Mycoplasma gallisepticum-infected RAW264.7 cells.

Toll-like receptor 2 (TLR2) plays a crucial role in early innate immune response of host to various microorganisms. Mycoplasma gallisepticum (MG) is one of the major pathogen that can cause chronic respiratory diseases in chickens, but the molecular mechanism of MG infection still remained unclear. In this study, we examined the typical hallmarks of autophagy and multiple signaling pathways by western blot, immunofluorescence microscopy and electron microscopy. The results indicated that infection of mouse macrophage cell line RAW264.7 with MG activated autophagy and mitogen-activated protein kinases (MAPKs). Silencing of TLR2 by siRNA substantially down-regulated MG-triggered autophagy in macrophages, and markedly reduced MG-induced extracellular regulated protein kinase (ERK) in macrophages but did not down-regulate c-Jun N-terminal kinase (JNK) and p38. Importantly, in macrophages, inhibition of ERK by PD98059 (ERK inhibitor) also significantly attenuated the level of autophagy upon MG infection, and the simultaneous treatment of TLR2 siRNA and PD98059 showed a similar effect on MG-induced autophagy as compared with TLR2 siRNA treatment alone. These findings thus demonstrate that TLR2 may mediate MG-induced autophagy through ERK signaling pathway in macrophage.