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The future development of wearable/implantable sensing and medical devices relies on substrates with excellent flexibility, stability, biocompatibility, and self-powered capabilities. Enhancing the energy efficiency and convenience is crucial, and converting external mechanical energy into electrical energy is a promising strategy for long-term advancement. Poly(vinylidene fluoride) (PVDF), known for its piezoelectricity, is an outstanding representative of an electroactive polymer. Ingeniously designed PVDF-based polymers have been fabricated as piezoelectric devices for various applications. Notably, the piezoelectric performance of PVDF-based platforms is determined by their structural characteristics at different scales. This Review highlights how researchers can strategically engineer structures on microscopic, mesoscopic, and macroscopic scales. We discuss advanced research on PVDF-based piezoelectric platforms with diverse structural designs in biomedical sensing, disease diagnosis, and treatment. Ultimately, we try to give perspectives for future development trends of PVDF-based piezoelectric platforms in biomedicine, providing valuable insights for further research.
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Protein therapeutics are essential in treating various diseases, but their inherent biological instability and short circulatory half-lives in vivo pose challenges. Herein, a quantitative one-pot iterative living polymerization technique is reported towards precision control over the molecular structure and monomer sequence of protein-polymer conjugates, aiming to maximize physicochemical properties and biological functions of proteins. Using this quantitative one-pot iterative living polymerization technique, we successfully develop a series of sequence-controlled protein-multiblock polymer conjugates, enhancing their biostability, pharmacokinetics, cellular uptake, and in vivo biodistribution. All-atom molecular dynamics simulations are performed to disclose the definite sequence-function relationship of the bioconjugates, further demonstrating their sequence-encoded cellular uptake behavior and in vivo biodistribution in mice. Overall, this work provides a robust approach for creating precision protein-polymer conjugates with defined sequences and advanced functions as a promising candidate in disease treatment.
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Simulación de Dinámica Molecular , Polimerizacion , Polímeros , Animales , Ratones , Polímeros/química , Distribución Tisular , Proteínas/química , HumanosRESUMEN
Tissue-specific delivery of oligonucleotide therapeutics beyond the liver remains a key challenge in nucleic acid drug development. To address this issue, exploiting exosomes as a novel carrier has emerged as a promising approach for efficient nucleic acid drug delivery. However, current exosome-based delivery systems still face multiple hurdles in their clinical applications. Herein, this work presents a strategy for constructing a hybrid exosome vehicle (HEV) through a DNA zipper-mediated membrane fusion approach for tissue-specific siRNA delivery. As a proof-of-concept, this work successfully fuses a liposome encapsulating anti-NFKBIZ siRNAs with corneal epithelium cell (CEC)-derived exosomes to form a HEV construct for the treatment of dry eye disease (DED). With homing characteristics inherited from exosomes, the siRNA-bearing HEV can target its parent cells and efficiently deliver the siRNA payloads to the cornea. Subsequently, the NFKBIZ gene silencing significantly reduces pro-inflammatory cytokine secretions from the ocular surface, reshapes its inflammatory microenvironment, and ultimately achieves an excellent therapeutic outcome in a DED mouse model. As a versatile platform, this hybrid exosome with targeting capability and designed therapeutic siRNAs may hold great potential in various disease treatments.
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Exosomas , Liposomas , Fusión de Membrana , ARN Interferente Pequeño , Exosomas/metabolismo , Exosomas/química , ARN Interferente Pequeño/metabolismo , Animales , Ratones , Liposomas/química , Síndromes de Ojo Seco/terapia , Humanos , Epitelio Corneal/metabolismo , Epitelio Corneal/patología , Silenciador del Gen , Córnea/metabolismoRESUMEN
Radionuclide-drug conjugates (RDCs) designed from small molecule or nanoplatform shows complementary characteristics. We constructed a new RDC system with integrated merits of small molecule and nanoplatform-based RDCs. Erlotinib was labeled with 131I to construct the bulk of RDC (131I-ER). Floxuridine was mixed with 131I-ER to develop a hydrogen bond-driving supermolecular RDC system (131I-ER-Fu NPs). The carrier-free 131I-ER-Fu NPs supermolecule not only demonstrated integrated merits of small molecule and nanoplatform-based RDC, including clear structure definition, stable quality control, prolonged circulation lifetime, enhanced tumor specificity and retention, and rapidly nontarget clearance, but also exhibited low biological toxicity and stronger antitumor effects. In vivo imaging also revealed its application for tumor localization of nonsmall cell lung cancer (NSCLC) and screening of patients suitable for epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. We considered that 131I-ER-Fu NPs showed potentials as an integrated platform for the radiotheranostics of NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Humanos , Animales , Ratones , Floxuridina/química , Floxuridina/farmacología , Radioisótopos de Yodo/química , Clorhidrato de Erlotinib/química , Clorhidrato de Erlotinib/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Radiofármacos/química , Radiofármacos/farmacología , Línea Celular Tumoral , Distribución Tisular , Ratones Desnudos , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Ratones Endogámicos BALB C , FemeninoRESUMEN
Membrane materials that resist nonspecific or specific adsorption are urgently required in widespread practical applications, such as water purification, food processing, and life sciences. In water purification, inevitable membrane fouling not only limits membrane separation performance, leading to a decline in both permeance and selectivity, but also remarkably increases operation requirements, and augments extra maintenance costs and higher energy consumption. In this work, we report a freestanding interfacial polymerization (IP) fabrication strategy for in situ creation of asymmetric block copolymer (BCP) nanofilms with antifouling properties, greatly outperforming the conventional surface post-modification approaches. The resultant free-standing asymmetric BCP nanofilms with highly-dense, highly-hydrophilic polyethylene glycol (PEG) brushes on one side, can be readily formed via a typical IP process of a well-defined double-hydrophilic BCP composed of a highly-efficient antifouling PEG block and a membrane-forming multiamine block. The asymmetric BCP nanofilms have been applied for efficient and sustainable natural water purification, demonstrating extraordinary antifouling capabilities accompanied with superior separation performance far beyond commercial polyamide nanofiltration membranes. The antifouling behaviors of asymmetric BCP nanofilms derived from the combined effect of the hydration layer, electrostatic repulsion and steric hindrance were further elucidated by water flux and fouling resistance in combination with all-atom molecular dynamics (MD) simulation. This work opens up a new avenue for the large-scale and low-cost creation of broad-spectrum, asymmetric membrane materials with diverse functional "defect-free" surfaces in real-world applications.
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Purpose: To evaluate VEGF-C-induced lymphoproliferation in conjunction with 5-fluorouracil (5-FU) antimetabolite treatment in a rabbit glaucoma filtration surgery (GFS) model. Methods: Thirty-two rabbits underwent GFS and were assigned to four groups (n = 8 each) defined by subconjunctival drug treatment: (a) VEGF-C combined with 5-FU, (b) 5-FU, (c) VEGF-C, (d) and control. Bleb survival, bleb measurements, and IOP were evaluated over 30 days. At the end, histology and anterior segment OCT were performed on some eyes. mRNA was isolated from the remaining eyes for RT-PCR evaluation of vessel-specific markers (lymphatics, podoplanin and LYVE-1; and blood vessels, CD31). Results: Qualitatively and quantitatively, VEGF-C combined with 5-FU resulted in blebs which were posteriorly longer and wider than the other conditions: vs. 5-FU (P = 0.043 for longer, P = 0.046 for wider), vs. VEGF-C (P < 0.001, P < 0.001) and vs. control (P < 0.001, P < 0.001). After 30 days, the VEGF-C combined with 5-FU condition resulted in longer bleb survival compared with 5-FU (P = 0.025), VEGF-C (P < 0.001), and control (P < 0.001). Only the VEGF-C combined with 5-FU condition showed a negative correlation between IOP and time that was statistically significant (r = -0.533; P = 0.034). Anterior segment OCT and histology demonstrated larger blebs for the VEGF-C combined with 5-FU condition. Only conditions including VEGF-C led to increased expression of lymphatic markers (LYVE-1, P < 0.001-0.008 and podoplanin, P = 0.002-0.011). Expression of CD31 was not different between the groups (P = 0.978). Conclusions: Adding VEGF-C lymphoproliferation to standard antimetabolite treatment improved rabbit GFS success and may suggest a future strategy to improve human GFSs.
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Modelos Animales de Enfermedad , Fluorouracilo , Glaucoma , Presión Intraocular , Trabeculectomía , Factor C de Crecimiento Endotelial Vascular , Animales , Conejos , Fluorouracilo/uso terapéutico , Fluorouracilo/farmacología , Glaucoma/cirugía , Glaucoma/fisiopatología , Glaucoma/tratamiento farmacológico , Factor C de Crecimiento Endotelial Vascular/metabolismo , Trabeculectomía/métodos , Presión Intraocular/fisiología , Antimetabolitos/farmacología , Antimetabolitos/uso terapéutico , Tomografía de Coherencia Óptica , Conjuntiva , ARN Mensajero/genéticaRESUMEN
In the field of contemporary medicine, inflammation has emerged as a significant concern in global public health. Among the current anti-inflammatory strategies, nanozymes possess distinctive advantages and demonstrate unexpected efficacy in combating inflammation. However, the indeterminate structures and limited enzyme-like activity exhibited by most developed nanozymes impede their clinical translation and therapeutic effectiveness. In this paper, we developed a nanozyme derived from a well-defined metal-organic cage (MOC). The oxidized MOC (MOC-O), containing pyridine nitrogen oxide moieties, exhibited effective cascade superoxide dismutase (SOD) and catalase (CAT)-like activities for scavenging reactive oxygen species (ROS). This ROS scavenging ability was confirmed through flow cytometry analysis using DCFH-DA in a hypoxia/reoxygenation (H/R) model, where MOC-O significantly alleviated oxidative stress. Furthermore, the administration of MOC-O resulted in preserved renal function during renal ischemia-reperfusion (I/R) injury due to downregulated oxidative stress levels and reduced cell apoptosis.
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Antioxidantes , Riñón , Estrés Oxidativo , Especies Reactivas de Oxígeno , Daño por Reperfusión , Superóxido Dismutasa , Daño por Reperfusión/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/patología , Animales , Antioxidantes/química , Antioxidantes/farmacología , Especies Reactivas de Oxígeno/metabolismo , Riñón/metabolismo , Estrés Oxidativo/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Ratones , Apoptosis/efectos de los fármacos , Catalasa/metabolismo , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , MasculinoRESUMEN
Bismuth (Bi) exhibits a high theoretical capacity, excellent electrical conductivity properties, and remarkable interlayer spacing, making it an ideal electrode material for supercapacitors. However, during the charge and discharge processes, Bi is prone to volume expansion and pulverization, resulting in a decline in the capacitance. Deposition of a nonmetal on its surface is considered an effective way to modulate its morphology and electronic structure. Herein, we employed the chemical vapor deposition technique to fabricate Se-decorated Bi nanosheets on a nickel foam (NF) substrate. Various characterizations indicated that the deposition of Se on Bi nanosheets regulated their surface morphology and chemical state, while sustaining their pristine phase structure. Electrochemical tests demonstrated that Se-decorated Bi nanosheets exhibited a 51.1% improvement in capacity compared with pristine Bi nanosheets (1313 F/g compared to 869 F/g at a current density of 5 A/g). The energy density of the active material in an assembled asymmetric supercapacitor could reach 151.2 Wh/kg at a power density of 800 W/kg. These findings suggest that Se decoration is a promising strategy to enhance the capacity of the Bi nanosheets.
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As an endogenous signaling molecule, carbon monoxide (CO) has emerged as an increasingly promising option regarding as gas therapy due to its positive pharmacological effects in various diseases. Owing to the gaseous nature and potential toxicity, it is particularly important to modulate the CO release dosages and targeted locations to elucidate the biological mechanisms of CO and facilitate its clinical applications. Based on these, diverse CO-releasing molecules (CORMs) have been developed for controlled release of CO in biological systems. However, practical applications of these CORMs are limited by several disadvantages including low stability, poor solubility, weak releasing controllability, random diffusion, and potential toxicity. In light of rapid developments and diverse advantages of nanomedicine, abundant nanomaterials releasing CO in controlled ways have been developed for therapeutic purposes across various diseases. Due to their nanoscale sizes, diversified compositions and modified surfaces, vast CO-releasing nanomaterials (CORNMs) have been constructed and exhibited controlled CO release in specific locations under various stimuli with better pharmacokinetics and pharmacodynamics. In this review, we present the recent progress in CORNMs according to their compositions. Following a concise introduction to CO therapy, CORMs and CORNMs, the representative research progress of CORNMs constructed from organic nanostructures, hybrid nanomaterials, inorganic nanomaterials, and nanocomposites is elaborated. The basic properties of these CORNMs, such as active components, CO releasing mechanisms, detection methods, and therapeutic applications, are discussed in detail and listed in a table. Finally, we explore and discuss the prospects and challenges associated with utilizing nanomaterials for biological CO release.
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Cisplatin (CDDP) is widely used as one kind of chemotherapy drugs in cancer treatment. It functions by interacting with DNA, leading to the DNA damage and subsequent cellular apoptosis. However, the presence of intracellular PARP1 diminishes the anticancer efficacy of CDDP by repairing DNA strands. Olaparib (OLA), a PARP inhibitor, enhances the accumulation of DNA damage by inhibiting its repair. Therefore, the combination of these two drugs enhances the sensitivity of CDDP chemotherapy, leading to improved therapeutic outcomes. Nevertheless, both drugs suffer from poor water solubility and limited tumor targeting capabilities. To address this challenge, we proposed the self-assembly of two drugs, CDDP and OLA, through hydrogen bonding to form stable and uniform nanoparticles. Self-assembled nanoparticles efficiently target tumor cells and selectively release CDDP and OLA within the acidic tumor microenvironment, capitalizing on their respective mechanisms of action for improved anticancer therapy. In vitro studies demonstrated that the CDDP-OLA NPs are significantly more effective than CDDP/OLA mixture and CDDP at penetrating cancer cells and suppressing their growth. In vivo studies revealed that the nanoparticles specifically accumulated at the tumor site and enhanced the therapeutic efficacy without obvious adverse effects. This approach holds great potential for enhancing the drugs' water solubility, tumor targeting, bioavailability, and synergistic anticancer effects while minimizing its toxic side effects.
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Photopolymerizations have garnered significant attention in polymer science due to their low polymerization temperature, high production efficiency, environmental friendliness, and spatial controllability. Despite these merits, the poor penetration and severe chemical damage from ultraviolet/visible (UV/Vis) light resources pose significant barriers to their success in conventional photopolymerizations. A recent breakthrough involving the utilization of near-infrared (NIR) laser with long wavelength has been exploited for diverse applications. With the combination of a NIR photosensitizer (PS), NIR-induced photopolymerizations have been successfully developed to alleviate the challenges in conventional methods. The enhancement of penetration depth and safety of NIR-induced photopolymerizations can contribute significantly to improving the efficiency of polymerization for production of intricate structures across various scales. In this concept, the typical types of PSs and polymerization mechanisms (PMs) within the NIR-induced photopolymerization systems have been classified in detail. Additionally, the applications of various polymers achieved by NIR-induced photopolymerizations are summarized. Furthermore, research directions and future challenges of this field are also discussed comprehensively.
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The construction of acyclic, non-adjacent 1,3-stereogenic centers, prevalent motifs in drugs and bioactive molecules, has been a long-standing synthetic challenge due to acyclic nucleophiles being distant from the chiral environment. In this study, we successfully synthesized highly valuable 1,2-bis(boronic) esters featuring acyclic and nonadjacent 1,3-stereocenters. Notably, this reaction selectively produces migratory coupling products rather than alternative deborylative allylation or direct allylation byproducts. This approach introduces a new activation mode for selective transformations of gem-diborylmethane in asymmetric catalysis. Additionally, we found that other gem-diborylalkanes, previously challenging due to steric hindrance, also successfully participated in this reaction. The incorporation of 1,2-bis(boryl)alkenes facilitated the diversification of the alkenyl and two boron moieties in our target compounds, thereby enabling access to a broad array of versatile molecules. DFT calculations were performed to elucidate the reaction mechanism and shed light on the factors responsible for the observed excellent enantioselectivity and diastereoselectivity. These were determined to arise from ligand-substrate steric repulsions in the syn-addition transition state.