Multifunctional High Entropy Alloys Enabled by Severe Lattice Distortion.

Since 2004, the design of high entropy alloys (HEAs) has generated significant interest within the materials science community due to their exceptional structural and functional properties. By incorporating multiple principal elements into a common lattice, it is possible to create a single-phase crystal with a highly distorted lattice. This unique feature enables HEAs to offer a promising combination of mechanical and physical properties that are not typically observed in conventional alloys. In this article, an extensive overview of multifunctional HEAs that exhibit severe lattice distortion is provided, covering the theoretical models that are developed to understand lattice distortion, the experimental and computational methods employ to characterize lattice distortion, and most importantly, the impact of severe lattice distortion on the mechanical, physical and electrochemical properties of HEAs. Through this review, it is hoped to stimulate further research into the study of distorted lattices in crystalline solids.

Metallic glass-based triboelectric nanogenerators.

Surface wear is a major hindrance in the solid/solid interface of triboelectric nanogenerators (TENG), severely affecting their output performance and stability. To reduce the mechanical input and surface wear, solid/liquid-interface alternatives have been investigated; however, charge generation capability is still lower than that in previously reported solid/solid-interface TENGs. Thus, achieving triboelectric interface with high surface charge generation capability and low surface wear remains a technological challenge. Here, we employ metallic glass as one triboelectric interface and show it can enhance the triboelectrification efficiency by up to 339.2%, with improved output performance. Through mechanical and electrical characterizations, we show that metallic glass presents a lower friction coefficient and better wear resistance, as compared with copper. Attributed to their low atomic density and the absence of grain boundaries, all samples show a higher triboelectrification efficiency than copper. Additionally, the devices demonstrate excellent humidity resistance. Under different gas pressures, we also show that metallic glass-based triboelectric nanogenerators can approach the theoretical limit of charge generation, exceeding that of Cu-based TENG by 35.2%. A peak power density of 15 MW·m-2 is achieved. In short, this work demonstrates a humidity- and wear-resistant metallic glass-based TENG with high triboelectrification efficiency.

In Situ Fabrication of Benzoquinone Crystal Layer on the Surface of Nest-Structural Ionohydrogel for Flexible "All-in-One" Supercapattery.

Flexible energy-storage devices lay the foundation for a convenient, advanced, fossil fuel-free society. However, the fabrication of flexible energy-storage devices remains a tremendous challenge due to the intrinsic dissimilarities between electrode and electrolyte. In this study, a strategy is proposed for fabricating a flexible electrode and electrolyte entirely inside a matrix. First, a nest-structural and redox-active ionohydrogel with excellent stretchability (up to 3000%) and conductivity (167.9 mS cm-1 ) is designed using a hydrated ionic liquid (HIL) solvent and chemical foaming strategy. The nest-structure ionohydrogel provides sufficient "highways" and "service area", and the cation in HIL facilitates the reaction, transportation, and deposition of benzoquinone. Subsequently, in situ, a novel benzoquinone crystal-gel interface (CGI) is in situ fabricated on the surface of the ionohydrogel through electrochemical deposition of benzoquinone. Thus, an integrated CGI-gel platform is successfully achieved with a middle body as an electrolyte and the surficial redox-active CGI membrane for electrochemical energy conversion and storage. Based on the CGI-gel platform, an extreme simple and effective "stick-to-use" strategy is proposed for constructing flexible energy-storage devices and then a series of flexible supercapatteries are fabricated with high stretchability and capacitance (5222.1 mF cm-2 at 600% strain), low self-discharge and interfacial resistance and a wearable, self-power and intelligent display.

Activated platelet membrane nanovesicles recruit neutrophils to exert the antitumor efficiency.

Platelets play a crucial role in the recruitment of neutrophils, mediated by P-selectin, CCL5, and ICAM-2. In this study, we prepared platelet membrane nanovesicles from activated platelets. Whether activated platelet membrane nanovesicles can recruit neutrophils has not been reported, nor has their role in antitumor immunity. The results of SDS-PAGE showed that the platelet membrane nanovesicles retained almost all the proteins of platelets. Western blotting showed that both the activated platelets and the platelet membrane nanovesicles expressed P-selectin, ICAM-2, and CCL5. In vivo results of a mouse model of breast cancer-transplanted tumor showed that tumor volume reduced significantly, Ki-67-positive tumor cells decreased, and TUNEL-positive tumor cells increased in tumors after treatment with activated platelet membrane nanovesicles (aPNs). After treatment with aPNs, not only the number of neutrophils, CD8+, CD4+ T cells, and B cells increased, but also IL-12, TNF-α, and IFN-γ levels elevated significantly in tumor tissues.

A "Square Box"-Structured Triboelectric Nanogenerator for Road Transportation Monitoring.

Nowadays, with the rapid development of e-commerce, the transportation of products has become more and more frequent. However, how to monitor the situation of products effectively and conveniently during road transportation is a long-standing problem. In order to meet this problem in practical applications, we fabricated a triboelectric nanogenerator sensor with a "square box" structure (S-TENG) for detecting the vibration suffered by vehicles. Specifically, with the spring installed in the S-TENG as a trigger, the two friction layers can contact and then separate to generate the real-time electrical signals when the S-TENG receives external excitation. The output voltage signals of the S-TENG under different vibration states were tested and the results demonstrated that the peak and zero positions of the open-circuit voltage-output curve are related to amplitude and frequency, respectively. In addition, the subsequent simulation results, obtained by ANSYS and COMSOL software, were highly consistent with the experimental results. Furthermore, we built a platform to simulate the scene of the car passing through speed bumps, and the difference in height and the number of speed bumps were significantly distinguished according to the output voltage signals. Therefore, the S-TENG has broad application prospects in road transportation.

Endothelial PERK-ATF4-JAG1 axis activated by T-ALL remodels bone marrow vascular niche.

The endoplasmic reticulum unfolded protein response (UPR) is a conserved adaptive signaling in ER homeostasis and has emerged as critical in highly proliferating cells and potential treatment target for acute T-cell lymphoblastic leukemia (T-ALL). Methods: in this study, we assessed the transcriptomic and phenotypic alterations in UPR response of the bone marrow endothelial cells (ECs) in mice engrafted with T-ALL and in bone marrow specimens from patients who have T-ALL. We used PERK inhibitor and generated endothelial specific PERK knockout mice to study the impact of PERK on leukemia progression and hematopoiesis. We performed chromatin immunoprecipitation (ChIP) to study the mechanistic regulation of JAG1 by ATF4. We characterized small extracellular vesicles (SEV) from leukemia-developing mice and studied the effect of SEVs on EC function. Results: we found that T-ALL development induced a robust activation of protein kinase RNA-like endoplasmic reticulum kinase (PERK)-dominant UPR in the bone marrow endothelial vascular niche. The activation of PERK-eIF2a-ATF4 axis remodels the vascular niche, upregulates angiogenic factors including VEGFα and ATF4-regulated JAG1, and suppresses the expression of SCF and CXCL12, which are important to HSC maintenance and regeneration. Further, targeting endothelial PERK significantly improved T-ALL outcome. EC-specific deletion of PERK abolished the aberrant JAG1 up-regulation, improved HSC maintenance, promoted leukemia apoptosis, and improved overall survival. Finally, we showed that small extracellular vesicles are critical mediators of endothelial PERK-eIF2a-ATF4 activation and JAG1 up-regulation in leukemia. Corroborating animal model studies, activation of PERK-ATF4-JAG1 is prominent in human T-ALL bone marrow and T-ALL xenografts. Conclusion: our studies thus revealed for the first time that the leukemia-initiated PERK-ATF4-JAG1 axis plays a critical role in the remodeling of the bone marrow vascular niche and that targeting vascular niche UPR is a potential therapeutic opportunity in T-ALL.

Development and Applications of Hydrogel-Based Triboelectric Nanogenerators: A Mini-Review.

In recent years, with the appearance of the triboelectric nanogenerator (TENG), there has been a wave of research on small energy harvesting devices and self-powered wearable electronics. Hydrogels-as conductive materials with excellent tensile properties-have been widely focused on by researchers, which encouraged the development of the hydrogel-based TENGs (H-TENGs) that use the hydrogel as an electrode. Due to the great feasibility of adjusting the conductivity and mechanical property as well as the microstructure of the hydrogels, many H-TENGs with excellent performance have emerged, some of which are capable of excellent outputting ability with an output voltage of 992 V, and self-healing performance which can spontaneously heal within 1 min without any external stimuli. Although there are numerous studies on H-TENGs with excellent performance, a comprehensive review paper that systematically correlates hydrogels' properties to TENGs is still absent. Therefore, in this review, we aim to provide a panoramic overview of the working principle as well as the preparation strategies that significantly affect the properties of H-TENGs. We review hydrogel classification categories such as their network composition and their potential applications on sensing and energy harvesting, and in biomedical fields. Moreover, the challenges faced by the H-TENGs are also discussed, and relative future development of the H-TENGs are also provided to address them. The booming growth of H-TENGs not only broadens the applications of hydrogels into new areas, but also provides a novel alternative for the sustainable power sources.

GOx/Hb Cascade Oxidized Crosslinking of Silk Fibroin for Tissue-Responsive Wound Repair.

Promising wound dressings can achieve rapid soft-tissue filling while refactoring the biochemical and biophysical microenvironment to recruit endogenous cells, facilitating tissue healing, integration, and regeneration. In this study, a tissue biomolecule-responsive hydrogel matrix, employing natural silk fibroin (SF) as a functional biopolymer and haemoglobin (Hb) as a peroxidase-like biocatalyst, was fabricated through cascade enzymatic crosslinking. The hydrogels possessed mechanical tunability and displayed adjustable gelation times. A tyrosine unit on SF stabilised the structure of Hb during the cascade oxidation process; thus, the immobilized Hb in SF hydrogels exhibited higher biocatalytic efficiency than the free enzyme system, which provided a continuously antioxidative system. The regulation of the dual enzyme ratio endowed the hydrogels with favourable biocompatibility, biodegradability, and adhesion strength. These multifunctional hydrogels provided a three-dimensional porous extracellular matrix-like microenvironment for promoting cell adhesion and proliferation. A rat model with a full-thickness skin defect revealed accelerated wound regeneration via collagen deposition, re-epithelialisation and revascularisation. Enzyme-loaded hydrogels are an attractive and high-safety biofilling material with the potential for wound healing, tissue regeneration, and haemostasis.

Zeaxanthin Attenuates the Vicious Circle Between Endoplasmic Reticulum Stress and Tau Phosphorylation: Involvement of GSK-3ß Activation.

BACKGROUND: Alzheimer's disease (AD) characterized by neurofibrillary tangles caused by hyperphosphorylated tau is the most common cause of dementia. Zeaxanthin (Zea), derived from fruits and vegetables, may reduce the risk of AD. Endoplasmic reticulum stress (ERS) might cause memory impairment in AD. OBJECTIVE: Here, we studied protective role of Zea on the relationship among ERS, activity of glycogen synthase kinase 3ß (GSK-3ß, tau phosphorylated kinase), and p-Tau (Ser 396 and Thr 231). METHODS: The results were obtained in non-RA and RA group by using different treatment, such as 9-cis-retinoic acid (RA), TM (ERS inducer), Zea, 4-PBA (ERS inhibitor), and SB216763 (GSK-3ß inhibitor). The methods included flow cytometry and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] for the detections of cell cycle and cell viability and western blot as a third measure of proteins in relation to ERS and tau phosphorylation. We have collected and analyzed all the data that suggested application of drugs for the treatment in non-RA and RA group. RESULTS: Zea displays its protection on TM-induced cell injury, upregulation of GRP78 expression, and change of GSK-3ß activity and tau phosphorylation when 4-PBA and SB216763 interfere with the process. CONCLUSION: These studies indicated that Zea is in vicious circle in ERS, GSK-3ß, and tau phosphorylation, and further reflect its potential value in AD.

Reversible Dendritic-Crystal-Reinforced Polymer Gel for Bioinspired Adaptable Adhesive.

High-strength and reversible adhesion technology, which is a universal phenomenon in nature but remains challenging for artificial synthesis, is essential for the development of modern science. Existing adhesive designs without interface versatility hinder their application to arbitrary surfaces. Bioinspired by creeper suckers, a crystal-fiber reinforced polymer gel adhesive with ultrastrong adhesion strength and universal interface adaptability is creatively prepared via introducing a room-temperature crystallizable solvent into the polymer network. The gel adhesive formed by hydrogen bonding interaction between crystal fibers and polymer network can successfully realize over 9.82 MPa reversible adhesion strength for rough interface and 406.87 J m-2 peeling toughness for skin tissue. In situ anchoring is achieved for adapting to different geometrical surfaces. The adhesion performance can be significantly improved with the further increase of the interfacial roughness and hydrophilicity, whose dissipation mechanism is simulated by finite element analysis. The melting-crystallization equilibrium of the crystal fibers is proved by synchrotron radiation scattering. Accordingly, reversible phase-transition triggered by light and heat can realize the controlled adhere-detach recycle. Later adjustments to the monomers or crystals are expected to broaden its applications to various fields such as bioelectronics, electronic processing, and machine handling.

Tissue Fluid Triggered Enzyme Polymerization for Ultrafast Gelation and Cartilage Repair.

The in situ gelation of injectable precursors is desirable in the field of tissue regeneration, especially in the context of irregular defect filling. The current driving forces for fast gelation include the phase-transition of thermally sensitive copolymers, click chemical reactions with tissue components, and metal coordination effect. However, the rapid formation of tough hydrogels remains a challenge. Inspired by aerobic metabolism, we herein propose a tissue-fluid-triggered cascade enzymatic polymerization process catalyzed by glucose oxidase and ferrous glycinate for the ultrafast gelation of acryloylated chondroitin sulfates and acrylamides. The highly efficient production of carbon radicals and macromolecules contribute to rapid polymerization for soft tissue augmentation in bone defects. The copolymer hydrogel demonstrated the regeneration-promoting capacity of cartilage. As the first example of using artificial enzyme complexes for in situ polymerization, this work offers a biomimetic approach to the design of strength-adjustable hydrogels for bio-implanting and bio-printing applications.

Novel Multifunctional Silver Nanocomposite Serves as a Resistance-Reversal Agent to Synergistically Combat Carbapenem-Resistant Acinetobacter baumannii.

In the face of the abundant production of various types of carbapenemases, the antibacterial efficiency of imipenem, seen as "the last line of defense", is weakening. Following, the incidence of carbapenem-resistant Acinetobacter baumannii (CRAB), which can generate antibiotic-resistant biofilms, is increasing. Based on the superior antimicrobial activity of silver nanoparticles against multifarious bacterial strains compared with common antibiotics, we constructed the IPM@AgNPs-PEG-NOTA nanocomposite (silver nanoparticles were coated with SH-PEG-NOTA as well as loaded by imipenem) whose core was a silver nanoparticle to address the current challenge, and IPM@AgNPs-PEG-NOTA was able to function as a novel smart pH-sensitive nanodrug system. Synergistic bactericidal effects of silver nanoparticles and imipenem as well as drug-resistance reversal via protection of the ß-ring of carbapenem due to AgNPs-PEG-NOTA were observed; thus, this nanocomposite confers multiple advantages for efficient antibacterial activity. Additionally, IPM@AgNPs-PEG-NOTA not only offers immune regulation and accelerates tissue repair to improve therapeutic efficacy in vivo but also can prevent the interaction of pathogens and hosts. Compared with free imipenem or silver nanoparticles, this platform significantly enhanced antibacterial efficiency while increasing reactive oxygen species (ROS) production and membrane damage, as well as affecting cell wall formation and metabolic pathways. According to the results of crystal violet staining, LIVE/DEAD backlight bacterial viability staining, and real-time quantitative polymerase chain reaction (RT-qPCR), this silver nanocomposite downregulated the levels of ompA expression to prevent formation of biofilms. In summary, this research demonstrated that the IPM@AgNPs-PEG-NOTA nanocomposite is a promising antibacterial agent of security, pH sensitivity, and high efficiency in reversing resistance and synergistically combatting carbapenem-resistant A. baumannii. In the future, various embellishments and selected loads for silver nanoparticles will be the focus of research in the domains of medicine and nanotechnology.

Zirconia Nanoparticles Induce HeLa Cell Death Through Mitochondrial Apoptosis and Autophagy Pathways Mediated by ROS.

Zirconia nanoparticles (ZrO2 NPs) are commonly used in the field of biomedical materials, but their antitumor activity and mechanism is unclear. Herein, we evaluated the anti-tumor activity of ZrO2 NPs and explored the anti-tumor mechanism. The results of in vitro and in vivo experiments showed that the level of intracellular reactive oxygen species (ROS) in HeLa cells was elevated after ZrO2 NPs treatment. Transmission electron microscopy (TEM) showed that after treatment with ZrO2 NPs, the mitochondria of HeLa cells were swollen, accompanied with the induction of autophagic vacuoles. In addition, flow cytometry analysis showed that the apoptotic rate of HeLa cells increased significantly by Annexin staining after treatment with ZrO2 NPs, and the mitochondrial membrane potential (MMP) was reduced significantly. The proliferation of HeLa cells decreased as indicated by reduced Ki-67 labeling. In contrast, TUNEL-positive cells in tumor tissues increased after treatment with ZrO2 NPs, which is accompanied by increased expression of mitochondrial apoptotic proteins including Bax, Caspase-3, Caspase-9, and Cytochrome C (Cyt C) and increased expression of autophagy-related proteins including Atg5, Atg12, Beclin-1, and LC3-II. Treating HeLa cells with N-acetyl-L-cysteine (NAC) significantly reduced ROS, rate of apoptosis, MMP, and in vivo anti-tumor activity. In addition, apoptosis- and autophagy-related protein expressions were also suppressed. Based on these observations, we conclude that ZrO2 NPs induce HeLa cell death through ROS mediated mitochondrial apoptosis and autophagy.

Construction of homologous cancer cell membrane camouflage in a nano-drug delivery system for the treatment of lymphoma.

BACKGROUND: Non-Hodgkin's lymphoma (NHL) possesses great heterogeneity in cytogenetics, immunophenotype and clinical features, and chemotherapy currently serves as the main treatment modality. Although employing monoclonal antibody targeted drugs has significantly improved its overall efficacy, various patients continue to suffer from drug resistance or recurrence. Chinese medicine has long been used in the treatment of malignant tumors. Therefore, we constructed a low pH value sensitivity drug delivery system based on the cancer cell membrane modified mesoporous silica nanoparticles loaded with traditional Chinese medicine, which can reduce systemic toxicity and improve the therapeutic effect for the targeted drug delivery of tumor cells. RESULTS: Accordingly, this study put forward the construction of a nano-platform based on mesoporous silica nanoparticles (MSNs) loaded with the traditional Chinese medicine isoimperatorin (ISOIM), which was camouflaged by the cancer cell membrane (CCM) called CCM@MSNs-ISOIM. The proposed nano-platform has characteristics of immune escape, anti-phagocytosis, high drug loading rate, low pH value sensitivity, good biocompatibility and active targeting of the tumor site, blocking the lymphoma cell cycle and promoting mitochondrial-mediated apoptosis. CONCLUSIONS: Furthermore, this study provides a theoretical basis in finding novel clinical treatments for lymphoma.

Construction of biomimetic silver nanoparticles in the treatment of lymphoma.

Lymphoma is a well-known malignant tumor in the human body. Although many anticancer drugs have been developed to improve the survival rate of patients, about 40% of patients continue to be recurrent or refractory, a key issue needing remedy. Therefore, it is necessary to identify alternative treatments to reduce the disease's mortality. To this effect, a new type of anti-lymphoma nanocomplex FA@RBCm-AgNPs was prepared using AgNPs as the core of nanoparticles along with the targeting molecule folic acid inserted erythrocyte membrane as the shell. The biomimetic properties of red blood cell membrane (RBCm) endow F-RAN with good biocompatibility as well as the ability to evade clearance of the reticuloendothelial system. In addition, F-RAN was modified with folic acid to actively and selectively identify tumor cells. In vivo and in vitro experiments demonstrate that F-RAN can inhibit lymphoma cells and induce apoptosis of stem cells while promoting apoptosis of lymphoma with no obvious side effects. Hence, F-RAN may serve as a new treatment for lymphoma.

A Nano-Traditional Chinese Medicine Against Lymphoma That Regulates the Level of Reactive Oxygen Species.

Jolkinolide B (JB) is a bioactive compound isolated from a Chinese herbal medicine that exerts antitumor activity. However, the anti-lymphoma effect of JB and its mechanism are yet to be revealed. Because free JB has poor pharmacokinetics and weak antitumor efficacy, we opted to use black phosphorus quantum dot (BPQD) nanomaterials as a drug loading platform to synthesize a nano-traditional Chinese medicine (nano-TCM) called BPQDs@JB. Compared with free JB, Raji cells administrated with BPQDs@JB exhibited the cell viability of 19.85 ± 1.02%, and the production of intracellular reactive oxygen species (ROS) was promoted. Likewise, BPQDs@JB was capable of rising the apoptosis rate of Raji cells to 34.98 ± 1.76%. In nude mice transplanted tumor model administrated with BPQDs@JB, the tumor tissue sections administrated with BPQDS@JB achieved a conspicuous red fluorescence, demonstrating the presence of most ROS production in the BPQDS@JB. TUNEL achieved a number of positive (brown) nuclei in vivo, revealing that BPQDS@JB could significantly induce tumor tissue apoptosis. As revealed from the mentioned results, BPQDs@JB can generate considerable ROS and interfere with the redox state to inhibit tumor. In brief, BPQDs@JB may be adopted as a treatment option for lymphoma.

Independent and Correlated Role of Apolipoprotein E ɛ4 Genotype and Herpes Simplex Virus Type 1 in Alzheimer's Disease.

The ɛ4 allele of the Apolipoprotein E (APOE) gene in individuals infected by Herpes simplex virus type 1 (HSV-1) has been demonstrated to be a risk factor in Alzheimer's disease (AD). APOE-ɛ4 reduces the levels of neuronal cholesterol, interferes with the transportation of cholesterol, impairs repair of synapses, decreases the clearance of neurotoxic peptide amyloid-ß (Aß), and promotes the deposition of amyloid plaque, and eventually may cause development of AD. HSV-1 enters host cells and can infect the olfactory system, trigeminal ganglia, entorhinal cortex, and hippocampus, and may cause AD-like pathological changes. The lifecycle of HSV-1 goes through a long latent phase. HSV-1 induces neurotropic cytokine expression with pro-inflammatory action and inhibits antiviral cytokine production in AD. It should be noted that interferons display antiviral activity in HSV-1-infected AD patients. Reactivated HSV-1 is associated with infectious burden in cognitive decline and AD. Finally, HSV-1 DNA has been confirmed as present in human brains and is associated with APOEɛ4 in AD. HSV-1 and APOEɛ4 increase the risk of AD and relate to abnormal autophagy, higher concentrations of HSV-1 DNA in AD, and formation of Aß plaques and neurofibrillary tangles.

Hofmeister-Effect-Guided Ionohydrogel Design as Printable Bioelectronic Devices.

Bioelectronic platforms convert biological signals into electrical signals by utilizing biocatalysts that provide tools to monitor the activity of cells and tissues. Traditional conducting materials such as solid conductors and conducting polymers are confronted with a great challenge in sophisticated production processes and mismatch at biological tissues-machine interfaces. Furthermore, the biocatalyst, the key functional component in the electron-transfer reaction for bio-signal detection denatures easily in an ionic conductive solution. Herein, a bionic strategy is elaborately developed to synthesize an ionohydrogel bioelectronic platform that possesses extracellular-matrix-like habitat by employing hydrated ionic liquids (HILs) as ionic solvent and bioprotectant. This strategy realizes an integration of ionic and enzymatic electronic circuits and minimization of the disparities between tissues and artificial machines. The Hofmeister effect of HILs on enzyme proteins and polymer chains ensures the high bioactivity of the enzymes and greatly improves the mechanical properties of the ionohydrogels. Moreover, hydrogen bonds formed by ILs, water, and polymer chains greatly improve the water-retention of the ionohydrogel and give it more practical significance. Consequently, the promising ionohydrogel is partly printed and fabricated into wearable devices as a pain-free humoral components monitor and a wireless motion-sensor.

Platelet-Membrane-Camouflaged Zirconia Nanoparticles Inhibit the Invasion and Metastasis of Hela Cells.

Zirconia nanoparticles (ZrO2 NPs) are widely applied in the field of biomedicine. In this study, we constructed a nanoplatform of ZrO2 NPs coated with a platelet membrane (PLTm), named PLT@ZrO2. PLTm nanovesicles camouflage ZrO2 NPs, prevent nanoparticles from being cleared by macrophage, and target tumor sites. Compared to ZrO2 alone, PLT@ZrO2 is better at inhibiting the invasion and metastasis of Hela cells in vitro and in vivo. In vitro, PLT@ZrO2 inhibited the growth and proliferation of Hela cells. Scratch-wound healing recovery assay demonstrated that PLT@ZrO2 inhibited Hela cells migration. Transwell migration and invasion assays showed that PLT@ZrO2 inhibited Hela cells migration and invasion. In vivo, PLT@ZrO2 inhibited the tumor growth of Xenograft mice and inhibited the lung and liver metastasis of Hela cells. Immunofluorescence and Western blotting results showed that anti-metastasis protein (E-cadherin) was upregulated and pro-metastasis proteins (N-cadherin, Smad4, Vimentin, E-cadherin,ß-catenin, Fibronectin, Snail, Slug, MMP2, Smad2) were down-regulated. Our study indicated that PLT@ZrO2 significantly inhibits tumor growth, invasion, and metastasis.

Smart Biomimetic Nanocomposites Mediate Mitochondrial Outcome through Aerobic Glycolysis Reprogramming: A Promising Treatment for Lymphoma.

Toxicity and drug resistance caused by chemotherapeutic drugs have become bottlenecks in treating tumors. The delivery of anticancer drugs based on nanocarriers is regarded as an ideal way to solve the aforementioned problems. In this study, a new antilymphoma nanodrug CD20 aptamer-RBCm@Ag-MOFs/PFK15 (A-RAMP) is designed and constructed, and it consists of two parts: (1) metal-organic frameworks Ag-MOFs (AM) loaded with tumor aerobic glycolysis inhibitor PFK15 (P), forming a core part (AMP); (2) targeted molecule CD20 aptamer (A) is inserted into the red blood cell membrane (RBCm) to form the shell part (A-R). A-RAMP under the guidance of CD20 aptamer actively targets B-cell lymphoma both in vitro and in vivo. As a result, A-RAMP not only significantly inhibits the effect on tumor growth but also shows no obvious side effects on the treated nude mice, indicating that A-RAMP can accurately target tumor cells, reprogram aerobic glycolysis, and exert synergistic antitumor effect by Ag+ and PFK 15. Furthermore, the antitumor mechanism of A-RAMP in vivo by apoptotic pathway and targeting metabonomics are explored. These results suggest that A-RAMP has a promising application prospect as an smart, safe, effective, and synergistic antilymphoma agent.