RESUMEN
The selective and sensitive sensing of neurochemicals is essential to decipher in-brain chemistry underlying brain pathophysiology. The recent development of flexible and multifunctional polymer-based fibers has been shown useful in recording and modulating neural activities, primarily electrical ones. In this study, we were able to realize fiber-based neurochemical sensing with high sensitivity and selectivity. We achieved a generalizable method to couple aptamers, a type of synthetic receptors on the carbon composites within fibers, as microsensors for highly selective neurochemical detection. Such an aptamer-coupled microelectrode fiber sensor (apta-µFS) enables simple, label-free, and sensitive dopamine (DA) detection down to 5 nM with ultrahigh specificity across major interferents. We succeeded in monitoring DA selectively within the living brain using our apta-µFS. We further showed the proof-of-concept of using microelectronic fiber-based toolsets to target neural pathways across electrical and chemical modalities. In summary, such fiber-based toolsets hold great potential to advance multimodal mechanistic understanding of brain pathophysiology.
Asunto(s)
Aptámeros de Nucleótidos , Técnicas Biosensibles , Microelectrodos , Técnicas Biosensibles/métodos , Encéfalo/metabolismo , Aptámeros de Nucleótidos/metabolismo , Polímeros/metabolismo , Dopamina/metabolismoRESUMEN
Oral cancer is a common malignancy worldwide, accounting for 1.9% to 3.5% of all malignant tumors. Transforming growth factor ß (TGF-ß), as one of the most important cytokines, is found to play complex and crucial roles in oral cancers. It may act in a pro-tumorigenic and tumor-suppressive manner; activities of the former include cell cycle progression inhibition, tumor microenvironment preparation, apoptosis promotion, stimulation of cancer cell invasion and metastasis, and suppression of immune surveillance. However, the triggering mechanisms of these distinct actions remain unclear. This review summarizes the molecular mechanisms of TGF-ß signal transduction, focusing on oral squamous cell and salivary adenoid systemic carcinomas as well as keratocystic odontogenic tumors. Both the supporting and contrary evidence of the roles of TGF-ß is discussed. Importantly, the TGF-ß pathway has been the target of new drugs developed in the past decade, some having demonstrated promising therapeutic effects in clinical trials. Therefore, the achievements of TGF-ß pathway-based therapeutics and their challenges are also assessed. The summarization and discussion of the updated knowledge of TGF-ß signaling pathways will provide insight into the design of new strategies for oral cancer treatment, leading to an improvement in oral cancer outcomes.
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Neoplasias de la Boca , Factor de Crecimiento Transformador beta , Humanos , Factor de Crecimiento Transformador beta/metabolismo , Transducción de Señal , Citocinas/farmacología , Carcinogénesis , Microambiente TumoralRESUMEN
The supramolecular polymeric radicals are developed to promote the generation efficiency and stability of naphthalenediimide (NDI) radical anions. To this end, a water-soluble bifunctional monomer bearing two naphthalene-viologen end groups and a NDI center is designed and synthesized. The supramolecular polymeric NDI radical anions are fabricated on the basis of host-guest complexation between the NDI-containing bifunctional monomer and cucurbit[8]uril (CB[8]) and followed by the photoinduced electron transfer process under UV light irradiation. The electrostatic effect of CB[8] and the bulky and rigid structure of supramolecular polymer are combined to stabilize the excited state of NDIs and NDI radical anions, contributing to the high enhancement of the formation of NDI radical anions with excellent stability. It is found that the highest occupied molecular orbital energy and lowest unoccupied molecular orbital energy of NDI are also lowered by the formation of supramolecular polymer. In addition, the supramolecular polymeric NDI radical anions could be utilized as a supramolecular photoreducing agent to reduce cytochrome C with a higher efficiency. It is anticipated that other radicals can also be stabilized through this strategy, and this line of research may lead to the development of novel polymeric radical materials.
Asunto(s)
Imidas , Naftalenos , Aniones , PolímerosRESUMEN
Functional siRNAs are employed as cross-linkers to direct the self-assembly of DNA-grafted polycaprolactone (DNA-g-PCL) brushes to form spherical and nanosized hydrogels via nucleic acid hybridization in which small interfering RNAs (siRNAs) are fully embedded and protected for systemic delivery. Owing to the existence of multivalent mutual crosslinking events inside, the crosslinked nanogels with tunable size exhibit not only good thermostability, but also remarkable physiological stability that can resist the enzymatic degradation. As a novel siRNA delivery system with spherical nucleic acid (SNA) architecture, the crosslinked nanogels can assist the delivery of siRNAs into different cells without any transfection agents and achieve the gene silencing effectively both inâ vitro and inâ vivo, through which a significant inhibition of tumor growth is realized in the anticancer treatment.
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ADN/química , Sistemas de Liberación de Medicamentos , Neoplasias Experimentales/tratamiento farmacológico , Polietilenglicoles/química , Polietileneimina/química , ARN Interferente Pequeño/administración & dosificación , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Células HeLa , Humanos , Ratones , Nanogeles , Neoplasias Experimentales/patología , Poliésteres/química , ARN Interferente Pequeño/química , ARN Interferente Pequeño/farmacología , ARN Interferente Pequeño/uso terapéuticoRESUMEN
By coating polydimethylsiloxane (PDMS) relief structures with a layer of opaque metal such as gold, the incident light is strictly allowed to pass through the nanoscopic apertures at the sidewalls of PDMS reliefs to expose underlying photoresist at nanoscale regions, thus producing subwavelength nanopatterns covering centimeter-scale areas. It was found that the sidewalls were a little oblique, which was the key to form the nanoscale apertures. Two-sided and one-sided subwavelength apertures can be constructed by employing vertical and oblique metal evaporation directions, respectively. Consequently, two-line and one-line subwavelength nanopatterns with programmable feature shapes, sizes, and periodicities could be produced using the obtained photomasks. The smallest aperture size and line width of 80 nm were achieved. In contrast to the generation of raised positive photoresist nanopatterns in phase shifting photolithography, the recessed positive photoresist nanopatterns produced in this study provide a convenient route to transfer the resist nanopatterns to metal nanopatterns. This nanolithography methodology possesses the distinctive advantages of simplicity, low cost, high throughput, and nanoscale feature size and shape controllability, making it a potent nanofabrication technique to enable functional nanostructures for various potential applications.
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Oro/química , Nanoestructuras/química , Nanotecnología/métodos , Impresión/métodos , Dimetilpolisiloxanos/química , Elasticidad , Humanos , Luz , Procesos Fotoquímicos , Propiedades de SuperficieRESUMEN
Developing a cost-effective nanolithography strategy that enables the production of subwavelength features with various shapes over large areas is a long-standing goal in the nanotechnology community. Herein, an inexpensive nanolithographic technique that combines the wafer-scale production capability of photolithography with the subwavelength feature size controllability of near-field photolithography was developed to fabricate centimeter-scale up to wafer-scale sub-100-nm variously shaped nanopatterns on surfaces. The wafer-scale elastomeric trench-based photomasks with subwavelength apertures created at the apexes were compatible with mask aligners, allowing for the production of wafer-scale subwavelength nanopatterns with adjustable feature sizes, shapes, and periodicities. The smallest feature sizes of 50 and 80 nm were achieved on positive tone and negative tone photoresist surfaces, respectively, which could be ascribed to a near-field optical effect. The fabricated centimeter-scale nanopatterns were functionalized to study cell-matrix adhesion and migration. Compared to currently developed nanolithographic methods that approach similar functionalities, this facile nanolithographic strategy combines the merits of low cost, subwavelength feature size, high throughput, and varied feature shapes, making it an affordable approach to be used in academic research for researchers at most institutions.
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Técnicas Electroquímicas , Oro/química , Nanoestructuras/química , Nanotecnología/métodos , Dimetilpolisiloxanos/química , Elasticidad , Nanotecnología/instrumentación , Tamaño de la Partícula , Polimetil Metacrilato/química , Impresión/métodosRESUMEN
To overcome the multidrug resistance (MDR) of P-glycoprotein (P-gp) substrate anticancer drugs, such as paclitaxel (PTX), a novel dual-functional prodrug, D-α-tocopherol polyethylene glycol succinate (TPGS) based PTX prodrug (TPGS-S-S-PTX), was synthesized here to fulfill the synergistic effect of P-gp inhibiting and intracellular redox-sensitive release. The prodrug could self-assemble into stable micelles in physiological environment with a diameter of â¼140 nm, while it disassociated in reductive condition and released PTX and TPGS active derivatives rapidly. High cell cytotoxicity in PTX-resistant human ovarian cell line A2780/T was observed with enhanced PTX accumulation due to the P-gp inhibition by the TPGS moiety. The IC50 of TPGS-S-S-PTX was 55% and 91% more effective than that of Taxol (clinical formulation of PTX) and uncleavable TPGS-C-C-PTX prodrug, respectively. This was found to be related with the increased apoptosis/necrosis and cell arrest in G2/M phase. In vivo evaluation of the TPGS-S-S-PTX prodrug exhibited an extended half-life, increased AUC (area under the concentration-time curve), enhanced tumor distribution and significant tumor growth inhibition with reduced side effects as compared to Taxol and TPGS-C-C-PTX. This prodrug has great potential in improving efficiency in the treatment of MDR tumors.
Asunto(s)
Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Paclitaxel/química , Paclitaxel/farmacología , Profármacos/química , Profármacos/farmacología , Vitamina E/análogos & derivados , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Química Farmacéutica/métodos , Portadores de Fármacos/química , Femenino , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Semivida , Humanos , Ratones , Micelas , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/metabolismo , Oxidación-Reducción , Polietilenglicoles/química , Ratas , Ratas Sprague-Dawley , Vitamina E/químicaRESUMEN
To overcome the P-glycoprotein (P-gp)-induced multidrug resistance (MDR) of cancer cells, a novel copolymer, chitosan-graft-D-α-tocopheryl polyethylene glycol 1000 (TPGS) (CT) was synthesized for doxorubicin (DOX) delivery by the P-gp inhibiting virtue of TPGS. DOX-loaded CT nanoparticles (NPs) were fabricated by a modified solvent extraction/evaporation method combined with ionic cross-linking to form a uniform particle size of 140-180 nm with â¼40% DOX loading efficiency. These drug-loaded CT NPs demonstrated a pH-responsive release behavior, and DOX was released more quickly under low pH values. Significant cell cytotoxicity was observed on the human hepatocarcinoma cells (HepG2 and BEL-7402) and human breast adenocarcinoma cells (MCF-7). The cell cytotoxicity and apoptosis of drug-resistant cells (MCF-7/DOX and BEL-7402/5-Fu), was greatly enhanced as compared to Adriamycin. The IC50 value showed that DOX-loaded CT NPs could be 1.5-199-fold more effective than Adriamycin. This can be attributed to the P-gp blocking and down-regulation of ATP levels by the CT NPs. The potential of these NPs to act as an oral delivery system was also investigated. Both the pharmacokinetic properties and in vivo antitumor activity of DOX-loaded CT NPs were improved compared with Adriamycin.
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Quitosano/química , Doxorrubicina/farmacocinética , Sistemas de Liberación de Medicamentos , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Nanopartículas/química , Vitamina E/análogos & derivados , Animales , Antibióticos Antineoplásicos/farmacocinética , Apoptosis/efectos de los fármacos , Western Blotting , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Proliferación Celular/efectos de los fármacos , Femenino , Citometría de Flujo , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Ratones , Nanopartículas/administración & dosificación , Polietilenglicoles/química , Polímeros/química , Polímeros/farmacocinética , Distribución Tisular , Células Tumorales Cultivadas , Vitamina E/química , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Nitric oxide (NO) has attracted much attention for its antitumor activity and synergistic effects when codelivered with anticancer agents. However, due to its chemical instability and short half-life, delivering gaseous NO directly to tumors is still challenging. Herein, we synthesized a NO releasing polymer, nitrate functionalized d-α-tocopheryl polyethylene glycol succinate (TNO3). TNO3 was able to self-assemble into stable micelles in physiological conditions, accumulate in tumors, and release â¼90% of NO content in cancer cells for 96 h. It further exhibited significant cancer cell cytotoxicity and apoptosis compared with nitroglycerine (GTN). Notably, TNO3 could also serve as an enhancer for the common chemotherapeutic drug doxorubicin (DOX). Codelivering TNO3 with DOX to hepatocarcinoma HepG2 cancer cells strengthened the cellular uptake of DOX and enabled the synergistic effect between NO and DOX to induce higher cytotoxicity (â¼6.25-fold lower IC50). Moreover, for DOX-based chemotherapy in tumor-bearing mice, coadministration with TNO3 significantly extended the blood circulation time of DOX (14.7-fold t1/2, 6.5-fold mean residence time (MRT), and 13.7-fold area under curve (AUC)) and enhanced its tumor accumulation and penetration, thus resulting in better antitumor efficacy. In summary, this new NO donor, TNO3, may provide a simple but effective strategy to enhance the therapeutic efficacy of chemotherapeutic drugs.
Asunto(s)
Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/tratamiento farmacológico , Doxorrubicina/administración & dosificación , Neoplasias Hepáticas/tratamiento farmacológico , Óxido Nítrico/metabolismo , Sarcoma 180/tratamiento farmacológico , Vitamina E/análogos & derivados , Animales , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacocinética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Doxorrubicina/química , Doxorrubicina/farmacocinética , Portadores de Fármacos , Femenino , Semivida , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Ratones , Micelas , Polietilenglicoles/química , Ratas Sprague-Dawley , Sarcoma 180/metabolismo , Sarcoma 180/patología , Distribución Tisular , Vitamina E/químicaRESUMEN
Coacervate droplets formed by liquid-liquid phase separation have attracted considerable attention due to their ability to enrich biomacromolecules while preserving their bioactivities. However, there are challenges to develop coacervate droplets as delivery vesicles for therapeutics resulting from the lack of physiological stability and inherent lack of membranes in coacervate droplets. Herein, polylysine-polynucleotide complex coacervate droplets with favorable physiological stability are formulated to efficiently and facilely concentrate small molecules, biomacromolecules and nanoparticles without organic solvents. To improve the biocompatibility, the PEGylated phospholipid membrane is further coated on the surface of the coacervate droplets to prepare coacervate-based artificial protocells (ArtPC) with membrane-like and cytoplasm-like structures. The ArtPC can confine the cyclic catalytic system of uricase and catalase inside to degrade uric acid and deplete the toxicity of H2O2. This biofunctional ArtPC effectively reduces blood uric acid levels and prevents renal injuries in mice with persistent hyperuricemia. The ArtPC-based therapy can bridge the disciplines of synthetic biology, pharmaceutics and therapeutics.
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Células Artificiales , Hiperuricemia , Animales , Ratones , Células Artificiales/química , Células Artificiales/metabolismo , Hiperuricemia/tratamiento farmacológico , Ácido Úrico , Peróxido de Hidrógeno , CitoplasmaRESUMEN
In this study, a biodegradable Schiff-base hydrogel urea, possessing substantial water retention and certain slow-release ability was designed and synthesized. Firstly, dialdehyde starch (DAS) and amine-terminated polyethylene glycol (PEG-(NH2)2) were synthesized using potato starch and polyethylene glycol. Then, a novel Schiff-base hydrogel (SH) was prepared through the in-situ reaction between the aldehyde group of DAS and the amino group of PEG-(NH2)2. Three SH based slow-release urea, designated as SHU1, SHU2, and SHU3 and distinguished by varying urea content, were obtained using SH as the substrate. Several characterizations and tests were conducted to determine the structure, thermal properties, morphology, swelling properties, sustainable use, water retention, and biodegradation properties of SH. Additionally, the slow-release behavior of SHU was studied. SEM results revealed that SH possessed a porous three-dimensional network structure, with a maximum water absorption capacity of 4440 % ± 6.23 %. Compared to pure urea, SHU exhibited better slow-release performance after 30 days of release in soil, with SHU1 having a residual nitrogen content of specifically 36.01 ± 0.57 % of the initial nitrogen content. A pot experiment with pakchoi substantiated the water retention and plant growth promotion properties of SHU. This study demonstrated a straightforward method for the preparation of starch-based Schiff-base hydrogels as fertilizer carriers.
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Hidrogeles , Urea , Hidrogeles/química , Urea/química , Almidón/química , Polietilenglicoles , Bases de Schiff/química , Agua/química , NitrógenoRESUMEN
Multidrug resistance (MDR) is one of the major obstacles to successful chemotherapy. Overexpression of drug efflux transporters such as P-glycoprotein (P-gp) is an important factor responsible for MDR. Herein, a novel copolymer, D-α-tocopheryl polyethylene glycol 1000-block-poly(ß-amino ester) (TPGS-b-PBAE, TP), was synthesized for overcoming multidrug resistance by the synergistic effect of the pH-sensitive behavior of PBAE and P-gp inhibiting activity of TPGS. Docetaxel (DTX) was chosen as the model drug. The resulting DTX-loaded nanoparticles were stable at pH 7.4, while they dissociated in a weakly acidic environment (pH 5.5) and released the incorporated DTX quickly. The DTX-loaded TP nanoparticles increased the cell cytotoxicity against both drug-sensitive human ovarian A2780 and drug-resistant A2780/T cells. The IC(50) of DTX-loaded TP against A2780/T cells was 100-fold lower than that of commercial DTX. This was associated with enhanced DTX-induced apoptosis and cell arrest in the G2/M phase. Furthermore, P-gp inhibition assays, including enhancement of the fluorescence intensity of rhodamine 123 and reduction of the intracellular ATP levels, confirmed the P-gp inhibition nature of the TP copolymer. The use of the TP copolymer is a new approach to improve the therapeutic effect of anticancer drugs in MDR tumors.
Asunto(s)
Antineoplásicos/química , Nanopartículas/química , Taxoides/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Docetaxel , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Concentración de Iones de Hidrógeno , Nanopartículas/metabolismo , Tamaño de la Partícula , Polietilenglicoles/química , Polímeros/química , Taxoides/metabolismo , Taxoides/farmacología , Vitamina E/análogos & derivados , Vitamina E/químicaRESUMEN
Polyphenols, a class of bioactive compounds with phenolic structures, are abundant in human diets. They have gained attention in biomedical fields due to their beneficial properties, including antioxidant, antibacterial, and anti-inflammatory activities. Therefore, polyphenols can prevent multiple chronic or infectious diseases and may help in the prevention of oral diseases. Oral health is crucial to our well-being, and maintaining a healthy oral microbiome is essential for preventing various dental and systemic diseases. However, the mechanisms by which polyphenols modulate the oral microbiota and contribute to oral health are still not fully understood, and the application of polyphenol products lies in different stages. This review provides a comprehensive overview of the advancements in understanding polyphenols' effects on oral health: dental caries, periodontal diseases, halitosis, and oral cancer. The mechanisms underlying the preventive and therapeutic effects of polyphenols derived from dietary sources are discussed, and new findings from animal models and clinical trials are included, highlighting the latest achievements. Given the great application potential of these natural compounds, novel approaches to dietary interventions and oral disease treatments may emerge. Moreover, investigating polyphenols combined with different materials presents promising opportunities for developing innovative therapeutic strategies in the treatment of oral diseases.
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Caries Dental , Microbiota , Animales , Humanos , Polifenoles/farmacología , Polifenoles/uso terapéutico , Polifenoles/química , Salud Bucal , Caries Dental/prevención & control , DietaRESUMEN
Through self-assembly, environmentally friendly cellulose nanocrystals (CNCs) can form films with a photonic crystal structure whose pitch size can be adjusted in a variety of ways at the fabrication stage. Moreover, the films exhibit response performance to multiple stimuli, which offers extensive applications. Poly(ethylene glycol) (PEG) and CNCs combine to form a smaller chiral nematic domain that develops a solid film with a uniform spiral structure when slowly dried. By changing the composition of CNCs and PEG, flexible and flat photonic composite films with uniform structural colors from blue to red are prepared. Benefiting from the change in pitch size by insertion and detachment of water molecules into the chiral nematic structure, CNCs films and CNC-PEG composite films exhibit a reversible structural color change in response to different humidity. In addition, the chiral nematic films formed by the combination of glycerol and CNCs have a reversible stimulation response to hydrochloric acid gas. Similarly, adjusting the ratio of glycerol can control the pitch size of the films and, thus, the reflective color. In summary, the pitch size of the photonic crystal structure of the films can be precisely tuned by regulating the additive ratio, and the two prepared films have reversible responses to humidity and hydrochloric acid gas, respectively. The CNC-based films show promise in the application of colorimetric biosensors.
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Celulosa , Glicerol , Celulosa/química , Humedad , Ácido Clorhídrico , Polietilenglicoles , AguaRESUMEN
Packaging multiple drugs into a nanocarrier with rational design to achieve synergistic cancer therapy remains a challenge due to the intrinsically varied pharmacodynamics of therapeutic agents. Especially difficult is combining small-molecule drugs and macromolecular biologics. Here, we successfully graft pheophorbide A (PPA) photosensitizers on DNA backbone at predesigned phosphorothioate modification sites. The synthesized four PPA-grafted DNAs are assembled into a tetrahedron framework, which further associates with a programmed death ligand-1 (PD-L1) small interfering RNA (siRNA) linker through supramolecular self-assembly to form an siRNA and PPA copackaged nanogel. With dual therapeutic agents inside, the nanogel can photodynamically kill tumor cells and induce remarkable immunogenic cell death. Also, it simultaneously silences the PD-L1 expression of the tumor cells, which substantially promotes the antitumor immune response and leads to an enhanced antitumor efficacy in a synergistic fashion.
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Neoplasias , Ácidos Nucleicos , Antígeno B7-H1/genética , Línea Celular Tumoral , Nanogeles , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Fármacos Fotosensibilizantes/farmacología , Polietilenglicoles , Polietileneimina , ARN Interferente Pequeño/genéticaRESUMEN
Small interfering RNA (siRNA) has been emerging as a highly selective and effective pharmaceutics for treating broad classes of diseases. However, the practical application of siRNA agent is often hampered by its poor crossing of the cellular membrane barrier and ineffective releasing from endosome to cytoplasm, leading to low gene silencing efficacy for clinical purposes. Thus far, cationic lipid and polymer-based vectors have been extensively explored for gene delivery. Yet condensing the rigid and highly negatively charged siRNA duplex to form a stable complex vehicle usually requires a large load of cationic carriers, prone to raising the toxicity issue for delivery. Herein, we develop a simple strategy that can efficiently condense the siRNAs into nanoparticle vehicles for target gene regulation. In this approach, we first employ a DNA-grafted polycaprolactone (DNA-g-PCL) brush as template to organize the small rigid siRNAs into a large brush-like structure (siRNA-brush) through nucleic acid hybridization. Then, the siRNA-brush assembly is condensed by an ionizable and biodegradable polymer (poly(ß-amino ester), PBAE) under acidic buffer condition to form a stable nanoparticle for siRNA delivery. Compared to the free siRNAs with poor complexing capability with PBAE, the large brush-like siRNA assemblies with more complicated topological architecture significantly promotes their electrostatic interaction with PBAE, enabling the formation of complexed nanoparticles at low weight ratio of polymer to siRNA. Additionally, PBAE/siRNA-brush complexes exhibit good biocompatibility and stability under physiological condition, as well as enhanced cellular internalization. When equipped with functional siRNAs, the obtained delivery system demonstrates excellent downregulation of target genes both in vitro and in vivo, through which the progression of hypertrophic scars can be retarded with negligible adverse effects in an xenografted mouse model.
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Ésteres , Polímeros , Animales , ADN , Silenciador del Gen , Ratones , Polímeros/química , ARN Interferente Pequeño/genéticaRESUMEN
Nowadays, bioelectronic devices are evolving from rigid to flexible materials and substrates, among which thermally-drawn-fiber-based bioelectronics represent promising technologies thanks to their inherent flexibility and seamless integration of multi-functionalities. However, electrochemical sensing within fibers remains a poorly explored area, as it imposes new demands for material properties-both the electrochemical sensitivity and the thermomechanical compatibility with the fiber drawing process. Here, we designed and fabricated microelectrode fibers made of carbon nanotube (CNT)-based hybrid nanocomposites and further evaluated their detailed electrochemical sensing performances. Carbon-black-impregnated polyethylene (CB-CPE) was chosen as the base material, into which CNT was loaded homogeneously in a concentration range of 3.8 to 10 wt%. First, electrical impedance characterization of CNT nanocomposites showed a remarkable decrease of the resistance with the increase in CNT loading ratio, suggesting that CNTs notably increased the effective electrical current pathways inside the composites. In addition, the proof-of-principle performance of fiber-based microelectrodes was characterized for the detection of ferrocenemethanol (FcMeOH) and dopamine (DA), exhibiting an ultra-high sensitivity. Additionally, we further examined the long-term stability of such composite-based electrode in exposure to the aqueous environment, mimicking the in vivo or in vitro settings. Later, we functionalized the surface of the microelectrode fiber with ion-sensitive membranes (ISM) for the selective sensing of Na+ ions. The miniature fiber-based electrochemical sensor developed here holds great potential for standalone point-of-care sensing applications. In the future, taking full advantage of the thermal drawing process, the electrical, optical, chemical, and electrochemical modalities can be all integrated together within a thin strand of fiber. This single fiber can be useful for fundamental multi-mechanistic studies for biological applications and the weaved fibers can be further applied for daily health monitoring as functional textiles.
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Nanocompuestos , Nanotubos de Carbono , Fibra de Carbono , Dopamina , Microelectrodos , Nanotubos de Carbono/químicaRESUMEN
Bovine pericardium (BP) is widely used in surgery and is commonly used as a patch after arteriotomy in cardiovascular surgery. BP patches have several advantages compared with prosthetic patches, including superior biocompatability, easy handling, less suture line bleeding, and possibly reduced rates of infection. These advantages of BP have led to its common use during carotid endarterectomy (CEA). However, long-term clinical results reported after CEA have suggested several issues that may be related to the patch, including restenosis, pseudoaneurysm formation, infection, fibrosis, calcification, and thrombosis. These complications may diminish the long-term efficacy of CEA and suggest potential areas for improvement of surgical patches. Understanding the mechanisms by which BP heals after patch angioplasty may lead to next generation tissue-engineered patches.
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Materiales Biocompatibles , Procedimientos Quirúrgicos Cardíacos/instrumentación , Enfermedades Cardiovasculares/cirugía , Pericardio/trasplante , Procedimientos Quirúrgicos Vasculares/instrumentación , Animales , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Bovinos , Endarterectomía Carotidea/instrumentación , Humanos , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares/efectos adversos , Cicatrización de HeridasRESUMEN
The effective identification and quantitative determination of Staphylococcus aureus is a major public health concern. Here, an innovative strategy that combines a bacteria-imprinted polydimethylsiloxane film for bacterial recognition and fluorescence resonance energy transfer platform for turn-on fluorescence sensing is demonstrated. The bacteria-imprinted polydimethylsiloxane film was facilely fabricated to generate corresponding specific sites on the polydimethylsiloxane surface via stamp imprinting using Staphylococcus aureus as template followed by modification with 1H,1H,2H,2H-perfluorooctyltriethoxysilane. The fluorescence resonance energy transfer platform was developed through electrostatic interaction between citrate-functional copper clusters and dopamine-stabilized gold nanoparticles. When the Staphylococcus aureus are present, the 1H,1H,2H,2H-perfluorooctyltriethoxysilane-modified bacteria-imprinted polydimethylsiloxane film can precisely capture the target; subsequently, the negatively charged bacteria compete with citrate-functional copper clusters and bind to dopamine-stabilized gold nanoparticles, leading to the fluorescence recovery of citrate-functional copper clusters. The entire detection process was achieved within 135 min, showing a wide linear calibration response from 10 to 1 × 107 cfu mL-1 with a low detection limit of 11.12 cfu mL-1. Furthermore, the recoveries from spiked samples were from 97.7 to 101.90% with relative standard derivations lower than 10%. The established label-free assay of measuring Staphylococcus aureus is rapid, sensitive, specific, and efficient.
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Transferencia Resonante de Energía de Fluorescencia/métodos , Colorantes Fluorescentes/química , Polímeros Impresos Molecularmente/química , Staphylococcus aureus/aislamiento & purificación , Animales , Ácido Cítrico/química , Cobre/química , Dimetilpolisiloxanos/química , Oro/química , Límite de Detección , Carne/microbiología , Nanopartículas del Metal/química , PorcinosRESUMEN
Two queen ant specimens, one alate and one dealate, from mid-Cretaceous (Late Albian-Early Cenomanian) Burmese amber are herein reported as belonging Haidomyrmex cerberus Dlussky, 1996. This is the first discovery and documentation of an alate queen in Haidomyrmex. Compared with workers of Haidomyrmex cerberus, alate and dealate queens are larger in body size, have smaller compound eyes, a longer antennal scape, more complex mandibles, and a relatively large-sized metasoma. It is hypothesized that these differences are due to caste differences.