Latest ArticlesTraditional therapies such as surgery and endocrine therapy no longer meet the clinical needs in prostate cancer treatment, and more effective treatments are urgently required. Recent studies have reported that targeted inhibition of the transcription factor cyclin dependent kinase 7 (CDK7) could effectively suppress prostate cancer progression. However, the toxicity of CDK7 inhibitors such as THZ1 is the main limitation of the clinical application. In this work, we synthesized Cys8E (C8E) nanoparticles (NPs) loaded with THZ1 (C8E@THZ1), a novel GSH-targeting and stimuli-responsive nano-delivery platform, and investigated its anti-tumor potential and biosafety properties. In vitro, C8E@THZ1 potently inhibited the proliferation and promoted the apoptosis of prostate cancer cells. On tumor-bearing mice, C8E@THZ1 inhibited tumors by up to 85%, while the damage of THZ1 to liver function was effectively avoided. These results confirmed that inhibition of CDK7 can effectively block the progression of prostate cancer, and that Cys8E NPs is a highly prospective delivery platform to promote the clinical application of CDK7 inhibitors.
The purification of low-grade coal-bed methane is extremely important, but challenging, due to the very similar physical properties of CH4 and N2. Herein, we proposed a dual polarization strategy by employing triazine and polyfluoride sites to construct polar pores in COF materials, achieving the efficient separation of CH4 from N2. As expected, the dual polarized F-CTF-1 and F-CTF-2 exhibit higher CH4 adsorption capacity and CH4/N2 selectivity than CTF-1 and CTF-2, respectively. Especially, the CH4 uptake capacity and CH4/N2 selectivity of F-CTF-2 is 1.76 and 1.42 times than that of CTF-2. This work not only developed promising COF materials for CH4/N2 separation, but also provided important guidance for the separation of other adsorbates with similar properties.
Searching for efficient nonprecious metal-based catalysts toward oxygen evolution reaction (OER) are of significance for seawater electrolysis. Herein, a core–shell-structured hybrid of cobalt phosphide nanowires@NiFe layered double hydroxide nanosheets grown on conductive nickel foam (CoP@NiFe LDH/NF) is prepared by a feasible approach at low temperature. The charming structure can provide numerous phosphide/hydroxide heterogenous interfaces, expose abundant active sites, and boost electron/mass transfer, synergistically enhancing catalytic OER activity. When employed as an electrocatalyst toward the OER, the resultant CoP@NiFe LDH/NF only requires a small overpotential of 287 mV to provide 300 mA/cm2 current density as well as long-time durability in 1.0 mol/L KOH seawater. The regulation of electronic states and surface reconstruction synergistically contribute to highly efficient seawater oxidation. This work provides an opportunity to construct efficient and inexpensive electrocatalysts for hydrogen production.
Satisfactory ionic conductivity, excellent mechanical stability, and high-temperature resistance are the prerequisites for the safe application of solid polymer electrolytes (SPEs) in all-solid-state lithium metal batteries (ASSLMBs). In this study, a novel poly(m-phenylene isophthalamide) (PMIA)-core/poly(ethylene oxide) (PEO)-shell nanofiber membrane and the functional Li6.4La3Zr1.4Ta0.6O12 (LLZTO) ceramic nanoparticle are simultaneously introduced into the PEO-based SPEs to prepare composite polymer electrolytes (CPEs). The core PMIA layer of composite nanofibers can greatly improve the mechanical strength and thermal stability of the CPEs, while the shell PEO layer can provide the 3D continuous transport channels for lithium ions. In addition, the introduction of functional LLZTO nanoparticle not only reduces the crystallinity of PEO, but also promotes the dissociation of lithium salts and releases more Li+ ions through its interaction with the Lewis acid-base of anions, thereby overall improving the transport of lithium ions. Consequently, the optimized CPEs present high ionic conductivity of 1.38×10−4 S/cm at 30 ℃, significantly improved mechanical strength (8.5 MPa), remarkable thermal stability (without obvious shrinkage at 150 ℃), and conspicuous Li dendrites blocking ability (> 1800 h). The CPEs also both have good compatibility and cyclic stability with LiFePO4 (> 2000 cycles) and high-voltage LiNi0.8Mn0.1Co0.1O2 (NMC811) (> 500 cycles) cathodes. In addition, even at low temperature (40 ℃), the assembled LiFePO4/CPEs/Li battery still can cycle stably. The novel design can provide an effective way to exploit high-performance solid-state electrolytes.
Tumor vascular normalization has emerged as a promising strategy for synergistic therapy recently. Based on the strategy of “fluorescence turn on-controllable release”, a novel bifunctional candidate was constructed based on previous developed vascular normalization inducer QDAU5, which could self-assemble to form functional enzyme infrared QDAU5 nanoparticles (FEIRQ NPs). Subsequently, biological evaluation demonstrated that the FEIRQ NPs could induce ferroptosis, endoplasmic reticulum stress, and antigen preconditioning and maturation of dendritic cells and CD8+ T cells, leading to excellent antitumor efficacy in the absence of cytotoxic drugs. Additionally, FEIRQ NPs show high fluorescence intensity upon exposure to the β-galactosidase (β-Gal) enzyme expressed in ovarian cancer, enabling real-time monitoring of therapeutic effects. Overall, our findings suggest a prospering strategy to early diagnosis and efficient therapy for ovarian cancer without cytotoxicity.
Photodynamic therapy (PDT) has emerged as a significant cancer therapy option. Currently, cation-based organic small molecule aggregation-induced emission (AIE) photosensitizers (PSs) attract the wide attention of many scientists, due to improved reactive oxygen species (ROS) production after cationization. However, such PSs tend to localize only the mitochondria, limiting the death way of tumor cells (usually apoptosis) during PDT process, which may affect the therapeutic effect under some circumstances. Herein, we designed a novel water-soluble three positive charge PS, TPAN-18F, which could be distributed uniformly in cell cytoplasm and had distribution in different sub-organelles (mitochondria, endoplasmic reticulum, lysosome). The experimental results showed that TPAN-18F-based PDT process can not only disrupt mitochondrial functions (reducing ATP production and destroying mitochondrial membrane potential), but also elevate the intracellular lipid peroxides (LPOs) level, which evoke the non-apoptotic death manner of tumor cells. Further, in vivo studies showed that TPAN-18F-based PDT could effectively inhibit tumor growth. Accordingly, we believe that the construction of TPAN-18F is suggestive for tumor non-apoptotic therapy.
KTi2(PO4)3 is a promising anode material for potassium storage, but suffers from low conductivity and difficult balance between high capacity and good structural stability. Herein, the Ti3C2T MXene is used as a multifunctional binder to fabricate the KTi2(PO4)3 electrode by the traditional homogenizing-coating method. The MXene nanosheets, together with the conductive agent super P nanoparticles, construct a multiple conductive network for fast electron/ion transfer and high electrochemical kinetics. Moreover, the network ensures the structural stability of the KTi2(PO4)3 electrode during the de-intercalation/intercalation of 4 K+ ions, which is beneficial for simultaneously achieving high capacity and good cycle performance. Therefore, the MXene-bonded KTi2(PO4)3 electrode delivers a reversible capacity of 255.2 mAh/g at 50 mA/g, outstanding rate capability with 132.3 mAh/g at 2 A/g, and excellent cycle performance with 151.6 mAh/g at 1 A/g after 2000 cycles. This work not only suggests a high-performance anode material for potassium-ion batteries, but also demonstrates that the MXene is a promising binder material for constructing conductive electrodes in rechargeable batteries.
Small molecule inhibitors have dominated the pharmaceutical landscape for a long time as the primary therapeutic paradigm targeting pathogenic proteins. However, their efficacy heavily relies on the amino acid composition and spatial constitution of proteins, rendering them susceptible to drug resistance and failing to target undruggable proteins. In recent years, the advent of targeted protein degradation (TPD) technology has captured substantial attention from both industry and academia. Employing an event-driven mode, TPD offers a novel approach to eliminate pathogenic proteins by promoting their degradation, thus circumventing the limitations associated with traditional small molecule inhibitors. Hydrophobic tag tethering degrader (HyTTD) technology represents one such TPD approach that is currently in the burgeoning stage. HyTTDs employ endogenous protein degradation systems to induce the degradation of target proteins through the proteasome pathway, which displays significant potential for medical value. In this review, we provide a comprehensive overview of the development history and the reported mechanism of action of HyTTDs. Additionally, we delve into the physiological roles, structure-activity relationships, and medical implications of HyTTDs targeting various disease-associated proteins. Moreover, we propose insights into the challenges that necessitate resolution for the successful development of HyTTDs, with the ultimate goal of initiating a new age of clinical treatment leveraging the immense potential of HyTTDs.
There is increasing evidence shows that either electrical stimulation (ES) or metal ion is an effective way to accelerate ulcerative wound healing. However, less attention is paid to investigating the synergistic effect between them. Herein, we explore the combined effects of ES and multiple metal ions on diabetic wound healing assisted by a triboelectric nanogenerator (TENG). Firstly, the novel Eggshell@CuFe2O4 nanocomposites (NCs) are prepared, which show unique structure and intrinsic antimicrobial properties. Subsequently, the as-prepared nanocomposites are embedded in oxidized starch hydrogel to form a multifunctional composite gel, which is further assembled into a wearable ionic triboelectric nanogenerator (iTENG) patch with polydimethylsiloxane (PDMS). It can convert the mechanical energy produced by a human body motion to electric energy and mediate the sequential release of metal ions (Fe2+/Ca2+/Cu2+), thereby resulting in the "cocktail effect" on impaired tissue. Under their effects, a satisfying healing result in diabetic mouse is identified, which can effectively accelerate wound healing process by relieving inflammation, promoting angiogenesis and collagen deposition. The work puts forward the cocktail effect of electric simulation coupled with the multiple metal ions, and opens up a new perspective in designing iTENG patch towards repair of hard-to-heal wounds.
Bladder cancer is a common malignant tumor of the urinary system with the potential to be treated by nano drug delivery system. The current work describes the synthesis and characterization of a novel nanomaterial to construct a nano-carrier based on 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphatecholine (POPC) loaded doxorubicin (DOX) and embedded with gold nanoparticles and poly(N-isopropyl acrylamide) (PNIPAM) (GNPS@PNIPAM-POPC-DOX, GPPD). The dual-sensitive nanosystem gives simultaneous photothermal treatment and chemotherapy for bladder cancer. In vitro and in vivo properties were assessed using bladder cancer cell lines and mice and GPPD system distribution, tumor inhibition, and biocompatibility are reported. The system had favorable stability, low biological toxicity, controlled release efficiency, photothermal synergistic action, efficient photothermal transition, and favorable tumor suppressive effects. As a result, GPPD is a potential therapeutic approach for bladder cancer.
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