Advancing Pore-Space-Partitioned Metal-Organic Frameworks with Isoreticular Cluster Concept.

Trigonal planar M3(O/OH) trimers are among the most important clusters in inorganic chemistry and are the foundational features of multiple high-impact MOF platforms. Here we introduce a concept called isoreticular cluster series and demonstrate that M3(O/OH), as the first member of a supertrimer series, can be combined with a higher hierarchical member (double-deck trimer here) to advance isoreticular chemistry. We report here an isoreticular series of pore-space-partitioned MOFs called M3M6 pacs made from co-assembly between M3 single-deck trimer and M3x2 double-deck trimer. Important factors were identified on this multi-modular MOF platform to guide optimization of each module, which enables the phase selection of M3M6 pacs by overcoming the formation of previously-always-observed same-cluster phases. The new pacs materials exhibit high surface area and high uptake capacity for CO2 and small hydrocarbons, as well as selective adsorption properties relevant to separation of industrially important mixtures such as C2H2/CO2 and C2H2/C2H4. Furthermore, new M3M6 pacs materials show electrocatalytic properties with high activity.

Effect of supervised exercise training on cardiovascular function in patients with intermittent claudication: a systematic review and meta-analysis of randomized controlled trials.

This study aimed to determine the effect of supervised exercise training (SET) on cardiovascular function in patients with intermittent claudication (IC). A systematic search in MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases was conducted. Primary outcomes were systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), rate pressure product (RPP), cardiac output (CO), peak oxygen consumption (VO2peak), and heart rate variability (HRV). Secondary outcomes were maximum walking distance (MWD) and pain-free walking distance (PFWD). Outcomes were reported as weighted mean difference (WMD) between the SET group and the control group and synthesized by using the random-effects model. Seventeen RCTs with a total of 936 patients were included in this review. SET resulted in significant improvements of SBP (WMD = - 7.40, 95% CI - 10.69 ~ - 4.11, p < 0.001, I2 = 15.2%), DBP (WMD = - 1.92, 95% CI - 3.82 ~ - 0.02, p = 0.048, I2 = 0.0%), HR (WMD = - 3.38, 95% CI - 6.30 ~ - 0.46, p = 0.023, I2 = 0.0%), RPP (WMD = - 1072.82, 95% CI - 1977.05 ~ - 168.59, p = 0.020, I2 = 42.7%), and VO2peak with plantar flexion ergometer exercise (WMD = 5.57, 95% CI 1.66 ~ 9.49, p = 0.005, I2 = 62.4%), whereas CO and HRV remained statistically unaltered. SET also improved MWD (WMD = 139.04, 95% CI 48.64 ~ 229.44, p = 0.003, I2 = 79.3%) and PFWD (WMD = 40.02, 95% CI 23.85 ~ 56.18, p < 0.001, I2 = 0.0%). In conclusion, SET is effective in improving cardiovascular function in patients with IC, which was confirmed on outcomes of cardiovascular function associated with exercise ability. The findings hold out that the standard therapy of SET can improve not only walking distance but also cardiovascular function in patients with IC.

Progress of Influenza Viruses and Inhibitors.

Influenza is an acute respiratory disease caused by influenza viruses. It has the characteristics of fast transmission and strong infectivity, and it does great harm to human health and survival. It is estimated that the seasonal influenza epidemics every year will cause about one billion cases of infections and hundreds of thousands of deaths worldwide, while influenza A virus is the leading cause of infection and death. Currently, the main drugs used in clinics to treat influenza viruses are neuraminidase inhibitors, and these drugs have shown excellent efficacy in treating influenza viruses. However, various mutant strains have developed resistance to these effective drugs in clinics (such as the subtype mutant strains of H274Y in H1N1 or H5N1 and E119V in H3N2 have developed resistance to Oseltamivir). Influenza viruses mutate frequently, and new viral strains are constantly discovered, and the pandemics will break out at any time. Therefore, it is urgent to develop efficient and broad-spectrum drugs to prevent and treat the influenza pandemic caused by the emerging new subtypes. This review focuses on describing the pandemic history, the structure, function and prevention methods of influenza viruses and the progress of the development of anti-influenza drugs, to provide the reference for prevention and treatment of influenza viruses and development of influenza virus inhibitors.

The Effects of MicroRNAs in the Development of Heart Failure.

PURPOSE OF REVIEW: Heart failure is a severe clinical syndrome with complex and unclarified mechanisms, and it poses a serious threat to human health. MicroRNA, a non-coding RNA, can directly bind to target genes and regulate their expression. The important role of microRNAs in the development of HF has become a hot topic of research in recent years. This paper summarizes and prospects the mechanisms of microRNAs in regulating cardiac remodeling during heart failure to provide reference ideas for further research and clinical treatment. RECENT FINDINGS: With extensive research, more target genes for microRNAs have been clarified. By modulating various molecules, microRNAs affect the contractile function of the myocardium and alter the process of myocardial hypertrophy, myocyte loss, and fibrosis, thereby interfering with the process of cardiac remodeling and exerting an important effect in the process of heart failure. Based on the above mechanism, microRNAs have promising applications in the diagnosis and treatment of heart failure. MicroRNAs form a complex post-transcriptional control mechanism of gene expression, and the increase or decrease of their content during heart failure largely alters the course of cardiac remodeling. By continuously identifying their target genes, it is expected to achieve more precise diagnosis and treatment of this important topic of heart failure.

Simultaneous Control of Flexibility and Rigidity in Pore-Space-Partitioned Metal-Organic Frameworks.

Flexi-MOFs are typically limited to low-connected (<9) frameworks. Here we report a platform-wide approach capable of creating a family of high-connected materials (collectively called CPM-220) that integrate exceptional framework flexibility with high rigidity. We show that the multi-module nature of the pore-space-partitioned pacs (partitioned acs net) platform allows us to introduce flexibility as well as to simultaneously impose high rigidity in a tunable module-specific fashion. The inter-modular synergy has remarkable macro-morphological and sub-nanometer structural impacts. A prominent manifestation at both length scales is the retention of X-ray-quality single crystallinity despite huge hexagonal c-axial contraction (≈ 30%) and harsh sample treatment such as degassing and sorption cycles. CPM-220 sets multiple precedents and benchmarks on the pacs platform in both structural and sorption properties. They possess exceptionally high benzene/cyclohexane selectivity, unusual C3H6 and C3H8 isotherms, and promising separation performance for small gas molecules such as C2H2/CO2.

A systematic review and meta-analysis of cold exposure and cardiovascular disease outcomes.

Background: Cold exposure has been considered an essential risk factor for the global disease burden, while its role in cardiovascular diseases is still underappreciated. The increase in frequency and duration of extreme cold weather events like cold spells makes it an urgent task to evaluate the effects of ambient cold on different types of cardiovascular disease and to understand the factors contributing to the population's vulnerability. Methods: In the present systematic review and meta-analysis, we searched PubMed, Scopus, and Cochrane. We included original research that explored the association between cold exposure (low temperature and cold spell) and cardiovascular disease outcomes (mortality and morbidity). We did a random-effects meta-analysis to pool the relative risk (RR) of the association between a 1°C decrease in temperature or cold spells and cardiovascular disease outcomes. Results: In total, we included 159 studies in the meta-analysis. As a result, every 1°C decrease in temperature increased cardiovascular disease-related mortality by 1.6% (RR 1.016; [95% CI 1.015-1.018]) and morbidity by 1.2% (RR 1.012; [95% CI 1.010-1.014]). The most pronounced effects of low temperatures were observed in the mortality of coronary heart disease (RR 1.015; [95% CI 1.011-1.019]) and the morbidity of aortic aneurysm and dissection (RR 1.026; [95% CI 1.021-1.031]), while the effects were not significant in hypertensive disease outcomes. Notably, we identified climate zone, country income level and age as crucial influential factors in the impact of ambient cold exposure on cardiovascular disease. Moreover, the impact of cold spells on cardiovascular disease outcomes is significant, which increased mortality by 32.4% (RR 1.324; [95% CI 1.2341.421]) and morbidity by 13.8% (RR 1.138; [95% CI 1.015-1.276]). Conclusion: Cold exposure could be a critical risk factor for cardiovascular diseases, and the cold effect varies between disease types and climate zones. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42022347247.

Highly Stable Fe/Co-TPY-MIL-88(NH2) Metal-Organic Framework (MOF) in Enzymatic Cascade Reactions for Chemiluminescence-Based Detection of Extracellular Vesicles.

Metal-Organic Frameworks (MOFs) can deliver many advantages when acting as enzyme mimics to assist with signal amplification in molecular detection: they have abundant active catalytic sites per unit volume of the material; their structures and elemental compositions are highly tunable, and their high specific surface area and porous property can assist with target separation and enrichment. In the present work, we have demonstrated that, by adding the pore partition agent, 2,4,6-tris(4-pyridyl)pyridine (TPY) during synthesis of the bimetallic Fe/Co-MIL-88(NH2) MOF to block the open metal sites, a highly porous MOF of Fe/Co-TPY-MIL-88(NH2) can be produced. This material also exhibits high stability in basic solutions and biofluids and possesses high peroxidase-mimicking activity, which can be utilized to produce long-lasting chemiluminescence (CL) from luminol and H2O2. Moreover, acting as the peroxidase-mimic, the Fe/Co-TPY-MIL-88(NH2) MOF can form the enzymatic cascade with glucose oxidase (GOx) for biomarker detection. When applied to detect extracellular vesicles (EVs), the MOF material and GOx are brought to the proximity on the EVs through two surface proteins, which triggers the enzyme cascade to produce high CL from glucose and luminol. EVs within the concentration range of 5 × 105 to 4 × 107 particles/mL can be detected with an LOD of 1 × 105 particles/mL, and the method can be used to analyze EV contents in human serum without sample preparation and EV purification. Overall, our work demonstrates that the high versatility and tunability of the MOF structures could bring in significant benefits to biosensing and enable ultrasensitive detection of biomarkers with judicious material designs.

The Effect of Carbon Doping on the Crystal Structure and Electrical Properties of Sb2Te3.

As a new generation of non-volatile memory, phase change random access memory (PCRAM) has the potential to fill the hierarchical gap between DRAM and NAND FLASH in computer storage. Sb2Te3, one of the candidate materials for high-speed PCRAM, has high crystallization speed and poor thermal stability. In this work, we investigated the effect of carbon doping on Sb2Te3. It was found that the FCC phase of C-doped Sb2Te3 appeared at 200 °C and began to transform into the HEX phase at 25 °C, which is different from the previous reports where no FCC phase was observed in C-Sb2Te3. Based on the experimental observation and first-principles density functional theory calculation, it is found that the formation energy of FCC-Sb2Te3 structure decreases gradually with the increase in C doping concentration. Moreover, doped C atoms tend to form C molecular clusters in sp2 hybridization at the grain boundary of Sb2Te3, which is similar to the layered structure of graphite. And after doping C atoms, the thermal stability of Sb2Te3 is improved. We have fabricated the PCRAM device cell array of a C-Sb2Te3 alloy, which has an operating speed of 5 ns, a high thermal stability (10-year data retention temperature 138.1 °C), a low device power consumption (0.57 pJ), a continuously adjustable resistance value, and a very low resistance drift coefficient.

Solvent-free Synthesis of Multi-Module Pore-Space-Partitioned Metal-Organic Frameworks for Gas Separation.

Multi-module design of framework materials with multiple distinct building blocks has attracted much attention because such materials are more amenable to compositional and geometrical tuning and thus offer more opportunities for property optimization. Few examples are known that use environmentally friendly and cost-effective solvent-free method to synthesize such materials. Here, we report the use of solvent-free method (also modulator-free) to synthesize a series of multi-module MOFs with high stability and separation property for C2 H2 /CO2 . The synthesis only requires simple mixing of reactants and short reaction time (2 h). Highly porous and stable materials can be made without any post-synthetic activation. The success of solvent-free synthesis of multi-module MOFs reflects the synergy between different modules, resulting in stable pore-partitioned materials, despite the fact that other competitive crystallization pathways with simpler framework compositions also exist.

Cross-task specificity and within-task invariance of cognitive control processes.

Cognitive control involves flexibly combining multiple sensory inputs with task-dependent goals during decision making. Several tasks involving conflicting sensory inputs and motor outputs have been proposed to examine cognitive control, including the Stroop, Flanker, and multi-source interference task. Because these tasks have been studied independently, it remains unclear whether the neural signatures of cognitive control reflect abstract control mechanisms or specific combinations of sensory and behavioral aspects of each task. To address these questions, we record invasive neurophysiological signals from 16 patients with pharmacologically intractable epilepsy and compare neural responses within and between tasks. Neural signals differ between incongruent and congruent conditions, showing strong modulation by conflicting task demands. These neural signals are mostly specific to each task, generalizing within a task but not across tasks. These results highlight the complex interplay between sensory inputs, motor outputs, and task demands underlying cognitive control processes.

Developing Water-Stable Pore-Partitioned Metal-Organic Frameworks with Multi-Level Symmetry for High-Performance Sorption Applications.

A new perspective is proposed in the design of pore-space-partitioned MOFs that is focused on ligand symmetry properties sub-divided here into three hierarchical levels: 1) overall ligand, 2) ligand substructure such as backbone or core, and 3) the substituent groups. Different combinations of the above symmetry properties exist. Given the close correlation between nature of chemical moiety and its symmetry, such a unique perspective into ligand symmetry and sub-symmetry in MOF design translates into the influences on MOF properties. Five new MOFs have been prepared that exhibit excellent hydrothermal stability and high-performance adsorption properties with potential applications such as C3 H6 /C2 H4 and C2 H2 /CO2 selective adsorption. The combination of high stability with high benzene/cyclohexane selectivity of ≈13.7 is also of particular interest.

Functionalized biomimetic nanoparticles combining programmed death-1/programmed death-ligand 1 blockade with photothermal ablation for enhanced colorectal cancer immunotherapy.

Immune checkpoint blockade therapy targeting programmed death-1 (PD-1) or its major ligand programmed death-ligand 1 (PD-L1) has achieved remarkable success in the treatment of several tumors, including colorectal cancer. However, the efficacy of PD-1/PD-L1 inhibitors is limited in some colorectal cancers within the immunosuppressive tumor microenvironment (such as when there is a lack of immune cell infiltration). Herein, anti-PD-L1 functionalized biomimetic polydopamine-modified gold nanostar nanoparticles (PDA/GNS@aPD-L1 NPs) were developed for synergistic anti-tumor treatment by combining PD-1/PD-L1 blockade with photothermal ablation. PDA/GNS@aPD-L1 NPs were prepared by encapsulating photothermal nanoparticles (polydopamine-modified gold nanostar, PDA-GNS) with cell membrane isolated from anti-PD-L1 single-chain variable fragment (scFv) over-expressing cells. In addition to disrupting PD-1/PD-L1 immunosuppressive signals, the anti-PD-L1 scFv on the membrane of PDA/GNS@aPD-L1 NPs was conducive to the accumulation of PDA-GNS at tumor sites. Importantly, the tumor photothermal ablation induced by PDA-GNS could reverse the immunosuppressive tumor microenvironment, thereby further improving the efficiency of PD-1/PD-L1 blockade therapy. In this study, the synthetized PDA/GNS@aPD-L1 NPs exhibited good biocompatibility, efficient photothermal conversion ability, and enhanced tumor-targeting ability. In vivo studies revealed that a PDA/GNS@aPD-L1 NP-based therapeutic strategy significantly inhibited tumor growth, and prolonged overall survival by further promoting the maturation of dendritic cells (DCs), increasing the infiltration of CD8+T cells, and decreasing the number of immunosuppressive cells (such as regulatory T cells and myeloid-derived suppressive cells). Collectively, the developed PDA/GNS@aPD-L1 NP-based therapeutic strategy combines PD-1/PD-L1 blockade with photothermal ablation, which could remodel the tumor microenvironment for effective clinical colorectal cancer therapy. STATEMENT OF SIGNIFICANCE: Immunosuppressive tumor microenvironment is the main challenge facing programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) blockade therapy. By encapsulating photothermal nanoparticles (polydopamine-modified gold nanostar, PDA-GNS) with cell membrane over-expressing anti-PD-L1 single-chain variable fragment, we constructed anti-PD-L1 functionalized biomimetic nanoparticles (PDA/GNS@aPD-L1 NPs). By specific binding to the PD-L1 present on tumor cells, PDA/GNS@aPD-L1 NPs could disrupt PD-1/PD-L1 immunosuppression signaling, and effectively deliver PDA-GNS targeting to tumor sites. Additionally, PDA-GNS-mediated local photothermal ablation of tumors promoted the release of tumor-associated antigens and thus activated anti-tumor immune responses. Meanwhile, hyperthermia facilitates immune cell infiltration by increasing tumor vascular permeability. Therefore, PDA/GNS@aPD-L1 NPs could sensitize tumors to PD-1/PD-L1 blockade therapy by remodeling the immunosuppressive tumor microenvironment, which provides a new strategy for tumor treatment.

Mechanical Stretch Promotes Neurite Outgrowth of Primary Cultured Dorsal Root Ganglion Neurons via Suppression of Semaphorin 3A-Neuropilin-1/Plexin-A1 Signaling.

Significant attempts have been made to promote neuronal extension and migration in nerve development and regeneration. Although mechanical stretch induces persistent elongation of the axon, the underlying molecular mechanisms are not yet clear. Some axonal guidance cues secreted in the growth cone that affect the axonal growth could attract or repel axons in neurite connection. As semaphorin 3A (Sema3A) is an important repulsion guidance molecule, inhibition of Sema3A has been postulated to promote neuronal development. In this study, the effects of mechanical stretch on dorsal root ganglion neuronal growth and the underlying mechanisms were investigated by assessing the extension direction, neurite length, cell body size, mitochondrial membrane potential, and the expression of Sema3A and its receptors. Our results showed that cell viability significantly increased at tensile strains of 2.5, 5, and 10% for 4 h, with the most prominent effect at 5% tensile strain. Moreover, neurons migrated closer to the stretching direction at 5% tensile strain (0-12 h), while the neurons of the control group moved in a disorderly manner. Furthermore, Sema3A-Neuropilin-1/Plexin-A1 signaling pathway was found to be suppressed after mechanical stretch at 5% tensile strain for 4 h by immunofluorescence staining, immunoprecipitation, and western blot assay. Finally, a Sema3A-SiRNA (SiRNA = small interfering RNA) treatment led to remarkable guidance growth in the stretch-grown neurons. Importantly, there was significant decrease of repulsive cue Sema3A expression and remarkable increase of attractive molecule Netrin-1 expression after mechanical stretching treatment, which jointly promoted neurite outgrowth. This study provides a promising new approach for the development of mechanical stretching therapy or guidance factor-related drugs in injured neuronal regeneration.

In Situ Synthesized Homochiral Spiroborate Ester Metal-Organic Framework with Mono-, Di-, and Trivalent Cations.

We report here a one-step method for synthesizing multi-component and in-situ-formed homochiral spiroborate-ester-based metal-organic framework CPM-B1. This unique material successfully integrates COF fragment spiroborate ester within the MOF and simultaneously incorporate homochirality and helicity. In addition, CPM-B1 is a rare example of framework materials that results from the cooperative assembly of three charge-complementary cations: +1 (lithium), +2 (cobalt), and +3 (boron). The sophistication of the co-assembly is further highlighted by the three structural roles of lithium ions. This unique structure contributes to its multi-functional properties such as ionic conductivity and catalytic activity for oxygen reduction reaction (by CPM-B1 carbonized material) and provides a new path to develop MOF materials with complex secondary building units and multi-functional applications.

Bimetallic Metal-Organic Framework Fe/Co-MIL-88(NH2) Exhibiting High Peroxidase-like Activity and Its Application in Detection of Extracellular Vesicles.

Metal-organic frameworks (MOFs) have many attractive features, including tunable composition, rigid structure, controllable pore size, and large specific surface area, and thus are highly applicable in molecular analysis. Depending on the MOF structure, a high number of unsaturated metal sites can be exposed to catalyze chemical reactions. In the present work, we report that using both Co(II) and Fe(III) to prepare the MIL-88(NH2) MOF, we can produce the bimetallic MOF that can catalyze the conversion of 3,3',5,5″-tetramethylbenzidine (TMB) to a color product through a reaction with H2O2 at a higher reaction rate than the monometallic Fe-MIL-88(NH2). The Michaelis constants (Km) of the catalytic reaction for TMB and H2O2 are 3-5 times smaller, and the catalytic constants (kcat) are 5-10 times higher than those of the horseradish peroxidase (HRP), supporting ultrahigh peroxidase-like activity. These values are also much more superior to those of the HRP-mimicking MOFs reported previously. Interestingly, the bimetallic MOF can be coupled with glucose oxidase (GOx) to trigger the cascade enzymatic reaction for highly sensitive detection of extracellular vesicles (EVs), a family of important biomarkers. Through conjugation to the aptamer that recognizes the marker protein on EV surface, the MOF can help isolate the EVs from biological matrices, which are subsequently labeled by GOx via antibody recognition. The cascade enzymatic reaction between MOF and GOx enables the detection of EVs at a concentration as low as 7.8 × 104 particles/mL. The assay can be applied to monitor EV secretion by cultured cells and also can successfully detect the different EV quantities in the sera samples collected from cancer patients and healthy controls. Overall, we prove that the bimetallic Fe/Co-MIL-88(NH2) MOF, with its high peroxidase activity and high biocompatibility, is a valuable tool deployable in clinical assays to facilitate disease diagnosis and prognosis.

The Peripheral Circulating Exosomal microRNAs Related to Central Inflammation in Chronic Heart Failure.

Sympathetic hyperactivity plays an important role in the progression of chronic heart failure (CHF). It is reported that inflammation in the rostral ventrolateral medulla (RVLM), a key region for sympathetic control, excites the activity of neurons and leads to an increase in sympathetic outflow. Exosome, as the carrier of microRNAs (miRNAs), has the function of crossing the blood-brain barrier. The present study was designed to investigate the effect of exosomal miRNAs on central inflammation via peripheral-central interaction in CHF. The miRNA microarray detection was performed to compare the difference between circulating exosomes and the RVLM in CHF rats. It was shown that the expression of miR-214-3p was significantly up-regulated, whereas let-7g-5p and let-7i-5p were significantly down-regulated in circulating exosomes and the RVLM. Further studies in PC12 cells revealed that miR-214-3p enhanced the inflammatory response, while let-7g-5p and let-7i-5p reduced the neuroinflammation. The direct interaction between the miRNA and its inflammatory target gene (miR-214-3p, Traf3; let-7g-5p, Smad2; and let-7i-5p, Mapk6) was confirmed by the dual-luciferase reporter assay. These results suggest that the circulating exosomes participate in the enhancement of inflammatory response in the RVLM through their packaged miRNAs, which may further contribute to sympathetic hyperactivity in CHF.

The Influence of High-Energy Faceted TiO2 Supports on Co and Co-Ru Catalysts for Dry Methane Reforming.

The reforming of methane from biogas has been proposed as a promising method of CO2 utilization. Co-based catalysts are promising candidates for dry methane reforming. However, the main constraints limiting the large-scale use of Co-based catalysts are deactivation through carbon deposition (coking) and sintering due to weak metal-support interaction. We studied the structure-function properties and catalytic behavior of Co/TiO2 and Co-Ru/TiO2 catalysts using two different types of TiO2 supports, commercial TiO2 and faceted non-stoichiometric rutile TiO2 crystals (TiO2 *). The Co and Ru metal particles were deposited on TiO2 supports using a wet-impregnation method with the percentage weight loading of Co and Ru of 5% and 0.5%, respectively. The materials were characterized using SEM, STEM-HAADF, XRD, XPS and BET. The catalytic performance was studied using the CH4 : CO2 ratio of 3 : 2 to mimic the methane-rich biogas composition. Our results indicate that the addition of Ru to Co catalysts supported on TiO2 * reduces carbon deposition and influences oxygen mobility. Co and Co-Ru catalysts supported on TiO2 * has superior activity with the highest conversion of CO2 and CH4 of 34.7% and 23.5%, respectively. Despite the improved performance, the Co-Ru/TiO2 * catalyst has limited stability due to the proliferation of nanoparticle growth and TiOx layers on the surface of the nanoparticles indicating the prevalence of the strong-metal support interaction.

Nanovesicles derived from bispecific CAR-T cells targeting the spike protein of SARS-CoV-2 for treating COVID-19.

BACKGROUND: Considering the threat of the COVID-19 pandemic, caused by SARS-CoV-2, there is an urgent need to develop effective treatments. At present, neutralizing antibodies and small-molecule drugs such as remdesivir, the most promising compound to treat this infection, have attracted considerable attention. However, some potential problems need to be concerned including viral resistance to antibody-mediated neutralization caused by selective pressure from a single antibody treatment, the unexpected antibody-dependent enhancement (ADE) effect, and the toxic effect of small-molecule drugs. RESULTS: Here, we constructed a type of programmed nanovesicle (NV) derived from bispecific CAR-T cells that express two single-chain fragment variables (scFv), named CR3022 and B38, to target SARS-CoV-2. Nanovesicles that express both CR3022 and B38 (CR3022/B38 NVs) have a stronger ability to neutralize Spike-pseudovirus infectivity than nanovesicles that express either CR3022 or B38 alone. Notably, the co-expression of CR3022 and B38, which target different epitopes of spike protein, could reduce the incidence of viral resistance. Moreover, the lack of Fc fragments on the surface of CR3022/B38 NVs could prevent ADE effects. Furthermore, the specific binding ability to SARS-CoV-2 spike protein and the drug loading capacity of CR3022/B38 NVs can facilitate targeted delivery of remdesiver to 293 T cells overexpressing spike protein. These results suggest that CR3022/B38 NVs have the potential ability to target antiviral drugs to the main site of viral infection, thereby enhancing the antiviral ability by inhibiting intracellular viral replication and reducing adverse drug reactions. CONCLUSIONS: In summary, we demonstrate that nanovesicles derived from CAR-T cells targeting the spike protein of SARS-COV-2 have the ability to neutralize Spike-pseudotyped virus and target antiviral drugs. This novel therapeutic approach may help to solve the dilemma faced by neutralizing antibodies and small-molecule drugs in the treatment of COVID-19.