Latest ArticlesFMS-like tyrosine kinase 3 (FLT3) is a viable and important therapeutic target for acute myeloid leukemia (AML). FLT3 internal tandem duplication (FLT3-ITD) mutations have been identified in approximately 30% of AML patients, and are associated with unfavorable prognosis, higher risk of relapse, drug resistance, and poor clinical outcome. Even FLT3 inhibitors have demonstrated promising efficacy, they cannot cure AML or even significantly extend the lives of patients with FLT3-ITD mutations. This is partly because of poor water solubility, insufficient membrane penetration and short half-life of small molecule inhibitors. Besides, the presence of enzymes like CYP3A4 in bone marrow accelerate the elimination and metabolism of FLT3 inhibitors, resulting in low plasma concentrations and side effects. Here we report the erythrocyte membrane-camouflaged FLT3 inhibitor nanoparticles to enhance FLT3-ITD AML treatment. Briefly, we physically coextruded red blood cell (RBC) membrane vesicles with nanoparticles derived from FLT3 inhibitor F30 to obtain F30@RBC-M, which exhibited comparable potent FLT3-ITD inhibitory effects compared to free F30 in vitro, while displaying a higher potent antitumor efficacy in xenograft models due to the prolonged circulation properties. Furthermore, administration of F30@RBC-M significantly extended the survival of mice in a transplanted mouse model than F30 free drug. These findings suggest that RBC membrane-coated nanoparticles derived from FLT3 inhibitors hold promise as a tool to enhance the therapeutic efficacy to treat FLT3-ITD AML.
Two novel fungal metabolites, asperochones A and B, were obtained from an Aspergillus sp. Their structures were determined by 1D/2D nuclear magnetic resonance (NMR) spectroscopy, high resolution electrospray ionization mass spectroscopy (HRESIMS), and single-crystal X-ray diffraction analysis. Asperochone A possesses an intriguing skeleton bearing 5/6/6/6/7/5/5/5 octacyclic ring system, and asperochone B also exhibits an unusual carbon skeleton with five stereochiral centers. Their structures were proposed as heterotrimeric and heterodimeric products of aromatic polyketides. In addition, asperochone A exhibited a potential anti-tuberculosis effect since it showed a moderate potency against Mycobacterium smegmatis.
As one of the most promising adoptive T-cell therapies, chimeric antigen receptor T-cell (CAR-T) therapy has acquired Food and Drug Administration (FDA) approval for a variety of products and has been used successfully in the treatment of malignant hematological tumors. CAR-T therapy, on the other hand, faces a number of obstacles in the field of solid tumor therapy that limit its widespread clinical implementation. Significant advances in nanoparticle research in cancer therapy and immunotherapy have been made in recent years, providing novel strategies to address the challenges encountered by CAR-T therapy in the treatment of solid tumors. This review commences with a comprehensive explanation of the basic framework of CAR-T therapy as well as the challenges it faces in the treatment of solid tumors. Subsequently, we encapsulate a summary of the developmental research combining nanoparticles with CAR-T cells for the treatment of solid tumors, which includes gene transfection, cell activation and expansion, targeted infiltration, immune escape inhibition, and combination with other therapies. Coupled with the overview of the research progress, a discussion has been initiated on the challenges and perspectives of CAR-T based on nanoparticles.
Macrophages, as a subset of innate immune cells, play a pivotal role in the initiation, maintenance, and resolution of inflammatory responses during tissue damage repair, defense against infections, and tumor progression. However, the mechanisms by which macrophages regulate inflammation in acute myeloid leukemia (AML) and their involvement in the chemotherapeutic effect remain elusive. In this study, we have identified that AML cells stimulate macrophage expansion by activating the colony-stimulating factor 1 receptor (CSF1R) pathway. The expanded macrophages activate nuclear factor kappa-B (NFκB) to induce the expression of inflammatory factors, thereby maintaining leukemic cell quiescence and promoting cell survival following chemotherapy. Furthermore, we have successfully utilized a poly(ferulic acid) nanocarrier to selectively target macrophages for inhibiting the NFκB-mediated inflammation, ultimately enhancing chemotherapy efficacy against AML. Taken together, our findings highlight the crucial role of macrophage-induced inflammation in conferring chemoresistance to AML, and demonstrate the potential of a targeted nanocarrier specifically designed for inflammatory macrophages to improve the AML chemotherapeutic outcomes.
Single-atom catalysts were widely used to treat atmospheric pollution and alleviate energy crises through photocatalysis. However, how to prevent the aggregation of single atoms during the preparation and catalytic processes remained a great challenge. Herein, a novel ultrathin two-dimensional porphyrin-based single-atom photocatalyst Ti-MOF (abbreviated as TMPd) obtained through a simple hydrothermal synthesis strategy was used for photocatalytic hydrogen evolution and NO removal, in which the single-atom Pd tightly anchored in the center of porphyrin to ensure single-atom Pd stable existence. Compared with most reported MOFs-based photocatalysts, the TMPd showed an excellent hydrogen evolution rate (1.32 mmol g−1 h−1) and the NO removal efficiency (62%) under visible light irradiation. Aberration-corrected high-angle annular dark-field scanning transmission electron microscope (HAADF-STEM) and synchrotron-radiation-based X-ray absorption fine-structure spectroscopy (XAFS) proved that pd in TMPd existed in an isolated state, and the atomic force microscope (AFM) proved the ultrathin morphology of TMPd. DFT calculations had demonstrated that single-atom Pd could serve as the active center and more effectively achieve electron transfer, indicating that single-atom Pd played a vital role in photocatalytic hydrogen evolution. In addition, a possible photocatalytic pathway of NO removal was proposed based on ESR and in-situ infrared spectra, in which the catalysts anchored with single-atom Pd could produce more active substances and more effectively oxidize NO to NO2− or NO3−. The results suggested that coordinating single-atom metal species as the active site in the center of porphyrin could be a feasible strategy to obtain various ultrathin porphyrin-based single-atom photocatalysts to acquire excellent photocatalytic performance further.
Formaldehyde (HCHO) as an indoor air pollutant released by new furniture and decorative materials is of great concern. Developing a self-cleaning device to remove HCHO is an ideal way to improve indoor air quality. In this study, a self-cleaning window with a multilayered structure constructed from fluorine-doped tin oxide/bismuth tungstate/resorcinol-formaldehyde resin (FTO/Bi2WO6/RF) has been fabricated, which is capable of degrading HCHO in natural indoor condition. The as-fabricated device could utilize the natural room light and promote the generation and transfer of the photocatalytic carriers in Bi2WO6, which subsequently delivers a good catalytic oxygen reduction efficiency in RF to produce hydrogen peroxide (H2O2). The as-synthesized H2O2 could further split into hydroxyl radicals (•OH), then oxide the HCHO molecules in the air. The present study demonstrates a novel and efficient strategy to fabricate a transparent multifunctional window for self-cleaning indoor gaseous pollutants, the concept is of great importance to be expanded in a broad range of indoor furniture for in-house air pollution control.
Nitrogen-doped carbon loaded single-atom catalysts (SACs) are promising candidates for electrocatalytic conversion of CO2 into high-valuable chemicals, and the modification of catalysts by heteroatom-doping strategy is an effective approach to enhance the CO2 reduction performance. However, the large difference exists in atomic radius between nitrogen atoms and the doped heteroatoms may lead to the poor stability of active sites. In this study, we have synthesized a Ni single atom catalyst with S doping at the second-shell on the ultrathin carbon nanosheets support (Ni-N4-SC) by solid-phase pyrolysis. The S atom in the second-shell contributes to the higher efficiency of CO2 conversion at lower potentials while the Ni-N4-SC can be more stable. The experimental results and theoretical calculations indicate that the S atom in second-shell breaks the uniform charge distribution and reduces the free energy of hydrogenation, which can increase the adsorption of CO2, accelerate charge transfer, and reduce the reaction energy barrier. This work reveals the close relationship between the second-shell and the electrocatalytic activity of single atom sites, which also provides a new perspective to design efficient single atom catalysts.
Peroxymonosulfate (PMS) activation and photocatalysis are effective technologies to remove organic pollutants, but the adsorption effect of the catalyst is usually unheeded in degradation process. Herein, a bifunctional catalyst of amorphous MoSx (a-MoSx) with 3D layer-by-layer superstructure was synthesized by assembling basic active units [Mo3S13]2- of MoS2. The large interlayer spacing and high exposure of active sites render a-MoSx to have excellent synergy of adsorption and photo-assisted PMS activation for tetracycline (TC) degradation. Experiments and DFT calculation show that TC can be efficiently enriched on a-MoSx by pore filling, π-π interaction, hydrogen bonding and high adsorption energy. Subsequently, PMS can be quickly activated through electron transfer with a-MoSx, resulting in high TC degradation efficiency of 96.6% within 20 min. In addition, the synergistic mechanism of adsorption and photo-assisted PMS activation was explored, and the degradation pathway of TC was expounded. This work is inspirational for constructing bifunctional catalysts with superior synergistic adsorption and catalytic capabilities to remove refractory organic pollutants in water.
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