RESUMEN
Manganese hydroxido (Mn-OH) complexes supported by a tripodal N,N',Nâ³-[nitrilotris(ethane-2,1-diyl)]tris(P,P-diphenylphosphinic amido) ([poat]3-) ligand have been synthesized and characterized by spectroscopic techniques including UV-vis and electron paramagnetic resonance (EPR) spectroscopies. X-ray diffraction (XRD) methods were used to confirm the solid-state molecular structures of {Na2[MnIIpoat(OH)]}2 and {Na[MnIIIpoat(OH)]}2 as clusters that are linked by the electrostatic interactions between the sodium counterions and the oxygen atom of the ligated hydroxido unit and the phosphinic (P=O) amide groups of [poat]3-. Both clusters feature two independent monoanionic fragments in which each contains a trigonal bipyramidal Mn center that is comprised of three equatorial deprotonated amide nitrogen atoms, an apical tertiary amine, and an axial hydroxido ligand. XRD analyses of {Na[MnIIIpoat(OH)]}2 also showed an intramolecular hydrogen bonding interaction between the MnIII-OH unit and P=O group of [poat]3-. Crystalline {Na[MnIIIpoat(OH)]}2 remains as clusters with Na+---O interactions in solution and is unreactive toward external substrates. However, conductivity studies indicated that [MnIIIpoat(OH)]- generated in situ is monomeric and reactivity studies found that it is capable of cleaving C-H bonds, illustrating the importance of solution-phase speciation and its direct effect on chemical reactivity. Synopsis: Manganese-hydroxido complexes were synthesized to study the influence of H-bonds in the secondary coordination sphere and their effects on the oxidative cleavage of substrates containing C-H bonds.
Asunto(s)
Complejos de Coordinación , Manganeso , Manganeso/química , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Lipooxigenasa/química , Lipooxigenasa/metabolismo , Espectroscopía de Resonancia por Spin del Electrón , Materiales Biomiméticos/química , Materiales Biomiméticos/síntesis químicaRESUMEN
The synthesis of graphene quantum dots-like enriched with specific oxygenated groups (o-GQDs) exhibiting great catalytic performance offers a promising tool for diagnosis and biomedicine, but introducing specific oxygen groups remains a challenge. Here, we propose a mild synthetic protocol for producing regulated fluorescence emission (from blue to yellow) carbonyl functionalized GQDs with double catalytic function through Fe3O4-catalyzed hydroxyl radical (·OH) oxidation the precursors like graphene oxide, polyaniline (PANI) and polydopamine (PDA). The method can be carried out at room temperature than the traditional high-temperature oxidation in concentrated acid. Interestingly, o-GQDs exhibit excellent peroxidase (POD)- and ascorbate oxidase-like activity. XPS characterization showed a significant increase in carbonyl content in o-GQDs compared to the precursor, even a 14-fold increase in blue-emitting iron-doped GQDs (b-Fe-GQDs). The introduction of Fe3O4 during the synthesis process results in a minor degree of Fe doping, which enhances the catalytic activity of b-Fe-GQDs through coordination with N. Based on this feature, highly sensitive single-signal and ultra-selective dual-signal methods for alkaline phosphatase detection were developed. This low cost and safe synthesis strategy paves the way for practical usage of o-GQDs.
Asunto(s)
Grafito , Radical Hidroxilo , Puntos Cuánticos , Puntos Cuánticos/química , Grafito/química , Radical Hidroxilo/análisis , Radical Hidroxilo/química , Fluorescencia , Fosfatasa Alcalina/metabolismo , Fosfatasa Alcalina/química , Fosfatasa Alcalina/análisis , Indoles/química , Indoles/síntesis química , Catálisis , Materiales Biomiméticos/química , Materiales Biomiméticos/síntesis química , Espectrometría de Fluorescencia , Oxidación-ReducciónRESUMEN
The regeneration of demineralized enamel holds great significance in the treatment of dental caries. Amelogenin (Ame), an essential protein for mediating natural enamel growth, is no longer secreted after enamel has fully matured in childhood. Although biomimetic mineralization based on peptides or proteins has made significant progress, easily accessible, low-cost, biocompatible and highly effective Ame mimics are still lacking. Herein, we construct a series of amphiphilic branched polypeptides (CAMPs) by facile coupling of the Ame's C-terminal segment and poly(γ-benzyl-L-glutamate), which serves to simulate the Ame's hydrophobic N-terminal segment. Among them, CAMP15 is the best biomimetic mineralization template with great self-assembly performance to guide the oriented crystallization of hydroxyapatite and is capable of inhibiting the adhesion of Streptococcus mutans and Staphylococcus aureus on the enamel surfaces. This work highlights the potential application of amphiphilic branched polypeptide as Ame mimics in repairing defected enamel, providing a promising strategy for prevention and treatment of dental caries.
Asunto(s)
Amelogenina , Materiales Biomiméticos , Esmalte Dental , Péptidos , Streptococcus mutans , Amelogenina/química , Amelogenina/farmacología , Péptidos/química , Péptidos/farmacología , Péptidos/síntesis química , Esmalte Dental/química , Esmalte Dental/efectos de los fármacos , Streptococcus mutans/efectos de los fármacos , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Materiales Biomiméticos/síntesis química , Staphylococcus aureus/efectos de los fármacos , Animales , Propiedades de Superficie , Humanos , Adhesión Bacteriana/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis químicaRESUMEN
As one of the most lethal cardiovascular diseases, aortic dissection (AD) is initiated by overexpression of reactive oxygen species (ROS) in the aorta that damages the vascular structure and finally leads to massive hemorrhage and sudden death. Current drugs used in clinics for AD treatment fail to efficiently scavenge ROS to a large extent, presenting undesirable therapeutic effect. In this work, a nanocatalytic antioxidation concept has been proposed to elevate the therapeutic efficacy of AD by constructing a cobalt nanocatalyst with a biomimetic structure that can scavenge pathological ROS in an efficient and sustainable manner. Theoretical calculations demonstrate that the antioxidation reaction is catalyzed by the redox transition between hydroxocobalt(III) and oxo-hydroxocobalt(V) accompanied by inner-sphere proton-coupled two-electron transfer, forming a nonassociated activation catalytic cycle. The efficient antioxidation action of the biomimetic nanocatalyst in the AD region effectively alleviates oxidative stress, which further modulates the aortic inflammatory microenvironment by promoting phenotype transition of macrophages. Consequently, vascular smooth muscle cells are also protected from inflammation in the meantime, suppressing AD progression. This study provides a nanocatalytic antioxidation approach for the efficient treatment of AD and other cardiovascular diseases.
Asunto(s)
Antioxidantes , Disección Aórtica , Cobalto , Catálisis , Cobalto/química , Cobalto/farmacología , Disección Aórtica/tratamiento farmacológico , Disección Aórtica/patología , Antioxidantes/química , Antioxidantes/farmacología , Animales , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Materiales Biomiméticos/síntesis química , Ratones , Especies Reactivas de Oxígeno/metabolismo , Humanos , Estrés Oxidativo/efectos de los fármacos , Nanopartículas del Metal/químicaRESUMEN
Enzyme immobilization within metal-organic frameworks (MOFs) is a promising solution to avoid denaturation and thereby utilize the desirable properties of enzymes outside of their native environments. The biomimetic mineralization strategy employs biomacromolecules as nucleation agents to promote the crystallization of MOFs in water at room temperature, thus overcoming pore size limitations presented by traditional postassembly encapsulation. Most biomimetic crystallization studies reported to date have employed zeolitic imidazole frameworks (ZIFs). Herein, we expand the library of MOFs suitable for biomimetic mineralization to include zinc(II) MOFs incorporating functionalized terephthalic acid linkers and study the catalytic performance of the enzyme@MOFs. Amine functionalization of terephthalic acids is shown to accelerate the formation of crystalline MOFs enabling new enzyme@MOFs to be synthesized. The structure and morphology of the enzyme@MOFs were characterized by PXRD, FTIR, and SEM-EDX, and the catalytic potential was evaluated. Increasing the linker length while retaining the amino moiety gave rise to a family of linkers; however, MOFs generated with the 2,2'-aminoterephthalic acid linker displayed the best catalytic performance. Our data also illustrate that the pH of the reaction mixture affects the crystal structure of the MOF and that this structural transformation impacts the catalytic performance of the enzyme@MOF.
Asunto(s)
Ácidos Carboxílicos , Cristalización , Estructuras Metalorgánicas , Temperatura , Agua , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/síntesis química , Ácidos Carboxílicos/química , Agua/química , Ácidos Ftálicos/química , Materiales Biomiméticos/química , Materiales Biomiméticos/síntesis química , Estructura Molecular , Zinc/química , Enzimas Inmovilizadas/química , Enzimas Inmovilizadas/metabolismo , Aminas/química , CatálisisRESUMEN
Recreating complex structures and functions of natural organisms in a synthetic form is a long-standing goal for humanity1. The aim is to create actuated systems with high spatial resolutions and complex material arrangements that range from elastic to rigid. Traditional manufacturing processes struggle to fabricate such complex systems2. It remains an open challenge to fabricate functional systems automatically and quickly with a wide range of elastic properties, resolutions, and integrated actuation and sensing channels2,3. We propose an inkjet deposition process called vision-controlled jetting that can create complex systems and robots. Hereby, a scanning system captures the three-dimensional print geometry and enables a digital feedback loop, which eliminates the need for mechanical planarizers. This contactless process allows us to use continuously curing chemistries and, therefore, print a broader range of material families and elastic moduli. The advances in material properties are characterized by standardized tests comparing our printed materials to the state-of-the-art. We directly fabricated a wide range of complex high-resolution composite systems and robots: tendon-driven hands, pneumatically actuated walking manipulators, pumps that mimic a heart and metamaterial structures. Our approach provides an automated, scalable, high-throughput process to manufacture high-resolution, functional multimaterial systems.
Asunto(s)
Impresión Tridimensional , Robótica , Humanos , Módulo de Elasticidad , Robótica/instrumentación , Robótica/métodos , Retroalimentación , Materiales Biomiméticos/síntesis química , Materiales Biomiméticos/químicaRESUMEN
Biological fluids, the most complex blends, have compositions that constantly vary and cannot be molecularly defined1. Despite these uncertainties, proteins fluctuate, fold, function and evolve as programmed2-4. We propose that in addition to the known monomeric sequence requirements, protein sequences encode multi-pair interactions at the segmental level to navigate random encounters5,6; synthetic heteropolymers capable of emulating such interactions can replicate how proteins behave in biological fluids individually and collectively. Here, we extracted the chemical characteristics and sequential arrangement along a protein chain at the segmental level from natural protein libraries and used the information to design heteropolymer ensembles as mixtures of disordered, partially folded and folded proteins. For each heteropolymer ensemble, the level of segmental similarity to that of natural proteins determines its ability to replicate many functions of biological fluids including assisting protein folding during translation, preserving the viability of fetal bovine serum without refrigeration, enhancing the thermal stability of proteins and behaving like synthetic cytosol under biologically relevant conditions. Molecular studies further translated protein sequence information at the segmental level into intermolecular interactions with a defined range, degree of diversity and temporal and spatial availability. This framework provides valuable guiding principles to synthetically realize protein properties, engineer bio/abiotic hybrid materials and, ultimately, realize matter-to-life transformations.
Asunto(s)
Materiales Biomiméticos , Biomimética , Polímeros , Conformación Proteica , Pliegue de Proteína , Proteínas , Secuencia de Aminoácidos , Polímeros/síntesis química , Polímeros/química , Proteínas/química , Materiales Biomiméticos/síntesis química , Materiales Biomiméticos/química , Líquidos Corporales/química , Citosol/química , Albúmina Sérica Bovina/química , Biología SintéticaRESUMEN
Synthetic iron-sulfur cubanes are models for biological cofactors, which are essential to delineate oxidation states in the more complex enzymatic systems. However, a complete series of [Fe4S4]n complexes spanning all redox states accessible by 1-electron transformations of the individual iron atoms (n = 0-4+) has never been prepared, deterring the methodical comparison of structure and spectroscopic signature. Here, we demonstrate that the use of a bulky arylthiolate ligand promoting the encapsulation of alkali-metal cations in the vicinity of the cubane enables the synthesis of such a series. Characterization by EPR, 57Fe Mössbauer spectroscopy, UV-visible electronic absorption, variable-temperature X-ray diffraction analysis, and cyclic voltammetry reveals key trends for the geometry of the Fe4S4 core as well as for the Mössbauer isomer shift, which both correlate systematically with oxidation state. Furthermore, we confirm the S = 4 electronic ground state of the most reduced member of the series, [Fe4S4]0, and provide electrochemical evidence that it is accessible within 0.82 V from the [Fe4S4]2+ state, highlighting its relevance as a mimic of the nitrogenase iron protein cluster.
Asunto(s)
Materiales Biomiméticos , Coenzimas , Hidrocarburos , Hierro , Nitrogenasa , Azufre , Materiales Biomiméticos/síntesis química , Materiales Biomiméticos/química , Coenzimas/síntesis química , Coenzimas/química , Hidrocarburos/síntesis química , Hidrocarburos/química , Hierro/química , Nitrogenasa/química , Oxidación-Reducción , Azufre/químicaRESUMEN
Oxidative degradation and rearrangement of polycyclic polyprenylated acylphloroglucinols (PPAPs) has created diverse families of unique natural products that are attractive targets for biomimetic synthesis. Herein, we report a racemic synthesis of hyperibrin A and its oxidative radical cyclization to give yezo'otogirin C, followed by epoxidation and House-Meinwald rearrangement to give hypermogin D. We also investigated the biomimetic synthesis of norascyronone A via a similar radical cyclization pathway, with unexpected results that give insight into its biosynthesis.
Asunto(s)
Productos Biológicos , Materiales Biomiméticos , Floroglucinol , Terpenos , Productos Biológicos/síntesis química , Productos Biológicos/química , Materiales Biomiméticos/síntesis química , Materiales Biomiméticos/química , Estructura Molecular , Floroglucinol/síntesis química , Floroglucinol/química , Terpenos/síntesis química , Terpenos/químicaRESUMEN
Cyclization reactions through cationic intermediates have become a highly valuable tool in organic synthesis. The use of alkynes as the terminating group in this type of cationic process offers wide synthetic possibilities because this group can serve as a precursor of different functionalities. This article shows relevant examples of cationic cyclization reactions with alkynes as terminating groups with the intention of demonstrating the potential of this type of process, particularly in the context of biomimetic synthesis of natural products.
Asunto(s)
Alquinos/química , Materiales Biomiméticos/síntesis química , Materiales Biomiméticos/química , Cationes/síntesis química , Cationes/química , CiclizaciónRESUMEN
The development of bioengineered nanoparticles has attracted considerable universal attention in the field of medical science and disease treatment. Current studies were executed to evaluate the hepatoprotective activity of biosynthesized silver nanoparticles (AgNPs). Their characterization was performed by UV-Visible analysis, fourier transform infrared spectroscopy, transmission electron microscopy (TEM), scanning electron microscope (SEM), and Zeta analyses. In in vivo studies, albino rats (180 ± 10 g) were persuaded with model hepatic toxicant N-nitrosodiethylamine (NDEA) and subsequently cotreated with Morus multicaulis at 100 mg/kg and AgNPs at 100 µg/kg dose. NDEA administration elevates the levels of liver function test biomarkers, which were reinstated to normal by cotreatment of test drugs. The oxidative stress and concentration of drug-metabolizing enzyme increase after induction of toxicant (NDEA), these markers are restored toward normal after cotreatment of nano-drug. Treatments of M. multicaulis extract did not show such significant protection. The NDEA-treated groups showed a significant rise in the level of cytokines (interleukin [IL-6] and IL-10) and reached normal with subsequent treatment with AgNPs. Histopathological studies also exhibited the curative effect of AgNPs in the same manner. Thus current results strongly suggest that biomimetic AgNPs could be used as an effective drug against hepatic alteration.
Asunto(s)
Materiales Biomiméticos , Enfermedad Hepática Inducida por Sustancias y Drogas , Dietilnitrosamina/toxicidad , Nanopartículas del Metal , Plata , Animales , Materiales Biomiméticos/síntesis química , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Masculino , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Ratas , Ratas Wistar , Plata/química , Plata/farmacologíaRESUMEN
Tendon injury is one of the most common musculoskeletal diseases in the world, severely challenging the public health care system. Electrospinning technique using polymer materials (i.e. polycaprolactone (PCL)) and hydrogels (i.e. sodium alginate (ALG)) contribute to the development and application of smart composite scaffolds in the tendon tissue engineering by advantageously integrating mechanical properties and biocompatibility. As a potential natural antioxidant, melatonin (MLT) represents the potential to promote tendon repair. Here, we develop an MLT-loaded PCL/ALG composite scaffold that effectively promotes tendon injury repair in vivo and in vitro via a controlled release of MLT, possibly mechanically relying on an antioxidant stress pathway. This biomimetic composite scaffold will be of great significance in the tendon tissue engineering.
Asunto(s)
Tendón Calcáneo/efectos de los fármacos , Alginatos/farmacología , Materiales Biomiméticos/farmacología , Hidrogeles/farmacología , Melatonina/farmacología , Poliésteres/farmacología , Tendón Calcáneo/lesiones , Tendón Calcáneo/patología , Alginatos/química , Animales , Materiales Biomiméticos/síntesis química , Materiales Biomiméticos/química , Células Cultivadas , Hidrogeles/química , Masculino , Melatonina/química , Poliésteres/química , Ratas , Ratas Sprague-Dawley , Ingeniería de Tejidos , Andamios del Tejido/químicaRESUMEN
Inspired by living organisms, soft robots are developed from intrinsically compliant materials, enabling continuous motions that mimic animal and vegetal movement1. In soft robots, the canonical hinges and bolts are replaced by elastomers assembled into actuators programmed to change shape following the application of stimuli, for example pneumatic inflation2-5. The morphing information is typically directly embedded within the shape of these actuators, whose assembly is facilitated by recent advances in rapid prototyping techniques6-11. Yet, these manufacturing processes have limitations in scalability, design flexibility and robustness. Here we demonstrate a new all-in-one methodology for the fabrication and the programming of soft machines. Instead of relying on the assembly of individual parts, our approach harnesses interfacial flows in elastomers that progressively cure to robustly produce monolithic pneumatic actuators whose shape can easily be tailored to suit applications ranging from artificial muscles to grippers. We rationalize the fluid mechanics at play in the assembly of our actuators and model their subsequent morphing. We leverage this quantitative knowledge to program these soft machines and produce complex functionalities, for example sequential motion obtained from a monotonic stimulus. We expect that the flexibility, robustness and predictive nature of our methodology will accelerate the proliferation of soft robotics by enabling the assembly of complex actuators, for example long, tortuous or vascular structures, thereby paving the way towards new functionalities stemming from geometric and material nonlinearities.
Asunto(s)
Robótica/instrumentación , Materiales Biomiméticos/síntesis química , Materiales Biomiméticos/química , Polivinilos/síntesis química , Polivinilos/química , Elastómeros de Silicona/síntesis química , Elastómeros de Silicona/química , Siloxanos/síntesis química , Siloxanos/químicaRESUMEN
Because of the blood-brain barrier and the high infiltration of glioma cells, the diagnostic accuracy and treatment efficiency of gliomas are still facing challenges. There is an urgent need to explore the integration of diagnostic and therapeutic methods to achieve an accurate diagnosis, guide surgery, and inhibit postoperative recurrence. In this work, we developed a macrophage loaded with a photothermal nanoprobe (MFe3O4-Cy5.5), which is able to cross the blood-brain barrier and accumulate into deep gliomas to achieve multimodal imaging and guided glioma surgery purposes. With desirable probing depth and high signal-to-noise ratio, Fe3O4-Cy5.5 can perform fluorescence, photoacoustic, and magnetic resonance imaging, which can distinguish brain tumors from the surrounding normal tissues and accurately guide glioma resection. Meanwhile, Fe3O4-Cy5.5 can effectively induce local photothermal therapy and inhibit the recurrence of glioma after surgery. These results demonstrate that the macrophage-mediated Fe3O4-Cy5.5, which can achieve a multimodal diagnosis, accurate imaging-guided surgery, and effective photothermal therapy, is a promising nanoplatform for gliomas.
Asunto(s)
Materiales Biomiméticos/farmacología , Neoplasias Encefálicas/terapia , Carbocianinas/farmacología , Glioma/terapia , Nanopartículas de Magnetita/química , Terapia Fototérmica , Animales , Materiales Biomiméticos/síntesis química , Materiales Biomiméticos/química , Barrera Hematoencefálica/efectos de los fármacos , Neoplasias Encefálicas/diagnóstico por imagen , Carbocianinas/química , Glioma/diagnóstico por imagen , Humanos , Macrófagos/efectos de los fármacos , Masculino , Ensayo de Materiales , Imagen Multimodal , Neoplasias Experimentales/diagnóstico por imagen , Neoplasias Experimentales/terapia , Tamaño de la Partícula , Porosidad , Ratas , Ratas Sprague-Dawley , Células Tumorales CultivadasRESUMEN
A membrane-lytic mechanism-based nanodrug is developed for drug-resistant tumor therapy by anchoring the small-molecule quaternary ammonium salt (QAS) on cross-linked (R)-(+)-lipoic acid nanoparticles (cLANs). The anchoring of QAS on the nanoparticle avoids the direct attack of long alkyl chains to the cell membrane under physiological conditions, while after entering tumor cells, the QAS is released from the dissociated cLANs, migrates to the phospholipid bilayer via electrostatic interaction, and destroys the cell membrane by the puncture of long alkyl chains. Since the QAS is designed to finally be hydrolyzed to amino acid betaine and food additive cetanol and the cLANs degrade to dihydrolipoic acid (DHLA, reduced form of dietary antioxidant lipoic acid in cells), the QAS@cLANs hold superior biosafety. In addition to the drug-resistant tumors, the QAS@cLANs demonstrate significant inhibition of metastatic tumors. This work provides not only a general and clinic-promising treatment for the refractory tumors but also opens a door for the medicinal use of QAS.
Asunto(s)
Antineoplásicos/farmacología , Antioxidantes/farmacología , Materiales Biomiméticos/farmacología , Reactivos de Enlaces Cruzados/farmacología , Nanopartículas/química , Compuestos de Amonio Cuaternario/farmacología , Ácido Tióctico/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Antioxidantes/síntesis química , Antioxidantes/química , Materiales Biomiméticos/síntesis química , Materiales Biomiméticos/química , Línea Celular , Supervivencia Celular/efectos de los fármacos , Reactivos de Enlaces Cruzados/síntesis química , Reactivos de Enlaces Cruzados/química , Relación Dosis-Respuesta a Droga , Resistencia a Antineoplásicos/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Ensayo de Materiales , Ratones , Estructura Molecular , Tamaño de la Partícula , Compuestos de Amonio Cuaternario/química , Sales (Química)/química , Sales (Química)/farmacología , Estereoisomerismo , Relación Estructura-Actividad , Ácido Tióctico/químicaRESUMEN
Fiber-based artificial muscles with excellent actuation performance are gaining great attention as soft materials for flexible actuators; however, current advances in fiber-based artificial muscles generally suffer from high cost, harsh stimulation regimes, limiting deformations, chemical toxicity, or complex manufacturing processing, which hinder the widespread application of those artificial muscles in engineering and practical usage. Herein, a facile cross-scale processing strategy is presented to construct commercially available nontoxic viscose fibers into fast responsive and humidity-driven yarn artificial muscles with a recorded torsional stroke of 1752° cm-1 and a maximum rotation speed up to 2100 rpm, which are comparable to certain artificial muscles made from carbon-based composite materials. The underlying mechanism of such outstanding actuation performance that begins to form at a mesoscale is discussed by theoretical modeling and microstructure characterization. The as-prepared yarn artificial muscles are further scaled up to large-sized fabric muscles through topological weaving structures by integrating different textile technologies. These fabric muscles extend the simple motion of yarn muscles into higher-level diverse deformations without any composite system, complex synthetic processing, and component design, which enables the development of new fiber-based artificial muscles for versatile applications, such as smart textiles and intelligent systems.
Asunto(s)
Materiales Biomiméticos/química , Músculos/química , Robótica , Textiles , Materiales Biomiméticos/síntesis química , Humanos , Tamaño de la PartículaRESUMEN
Chemotherapeutics often failed to elicit optimal antitumor responses against lung cancer due to their limited exposure and accumulation in tumors. To achieve an effective therapeutic outcome of paclitaxel (PTX) against metastatic lung cancer with attenuated systemic and local toxicities, pulmonary delivery of redox-responsive PTX dimeric nanoparticles (NPs) was introduced. PTX dimers conjugated through variable lengths of diacid linkers containing disulfide bonds (-SS-) (i.e., α-PTX-SS-PTX, ß-PTX-SS-PTX, and γ-PTX-SS-PTX) were initially synthesized and were subsequently self-assembled into uniform nanosized particles in the presence of vitamin E TPGS with high drug loading capacity (DE > 97%). Among various redox-sensitive scaffolds, ß-PTX-SS-PTX NPs exhibited an optimal reactive oxygen species/glutathione-responsive drug release behavior, causing a lower local toxicity profile of PTX in the lungs. The scaffolds also demonstrated excellent colloidal stability, cellular uptake efficiency, and discriminating cytotoxicity between cancer and healthy cells. Further, they depicted an improved lung retention as compared to the control nanovesicles (ß-PTX-CC-PTX) devoid of the redox-sensitive disulfide motif. In the B16F10 melanoma metastatic lung cancer mouse model, intratracheally delivered ß-PTX-SS-PTX NPs exhibited a stronger anticancer potential with reduced systemic toxicity as compared to Taxol intravenous injection containing an equivalent PTX dose. The PTX dimeric NPs could also dramatically reduce the local toxicity relative to Taxol following their pulmonary delivery. Thus, this study presents redox-responsive PTX dimeric NPs as a promising nanomedicine for improved therapeutic efficacy against metastatic lung cancer.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Materiales Biomiméticos/farmacología , Glutatión/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Nanopartículas/química , Paclitaxel/farmacología , Especies Reactivas de Oxígeno/metabolismo , Células A549 , Animales , Antineoplásicos Fitogénicos/síntesis química , Antineoplásicos Fitogénicos/química , Materiales Biomiméticos/síntesis química , Materiales Biomiméticos/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Dimerización , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Ensayo de Materiales , Ratones , Ratones Endogámicos C57BL , Estructura Molecular , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Paclitaxel/síntesis química , Paclitaxel/química , Ratas , Ratas Sprague-DawleyRESUMEN
Herein, a strategy for a metal ion-imprinted artificial antibody with recognition sites tagged by fluorescein was carried out to construct the selective sites with a sensitive optical response signal to the specific metal ion. The synthesized silica nanoparticles were modified by the derivative residue group of 3-aminopropyltriethoxysilane conjugated with a 4-chloro-7-nitro-1,2,3-benzoxadiazole (NBD-Cl) molecule through the hydrolysis and condensation reactions. The as-prepared silica nanoparticles were encapsulated by metal ion (Cu2+, Cd2+, Hg2+, and Pb2+)-imprinted polymers with nanostructured layers through the copolymerization of ethyl glycol dimethyl methacrylate (EGDMA) as a cross-linker, AIBN as an initiator, metal ions as template molecules, AA as a functional monomer, and acetonitrile as a solvent. The layers of molecular imprinted polymers (MIPs) with a core-shell structure removed template molecules by EDTA-2Na to retain the cavities and spatial sizes to match the imprinted metal ions. The microsensor arrays were achieved by the self-assembly technique of SiO2@MIP nanoparticles on the etched silicon wafer with regular dot arrays. The nanostructured-shell layers with fluorescence-tagged recognition sites rebound metal ions by the driving force of concentration difference demonstrates the high selective recognition and sensitive detection to heavy metal ions through the decline of fluorescence intensity. The LOD concentration for four metal ions is down to 10-9 mol·L-1. The method will provide biomimetic synthesis, analyte screen, and detection of highly dangerous materials in the environment for theoretical foundation and technological support.
Asunto(s)
Anticuerpos/química , Materiales Biomiméticos/química , Fluorescencia , Metales Pesados/análisis , Microtecnología , Nanoestructuras/química , Materiales Biomiméticos/síntesis química , Iones/análisis , Ensayo de Materiales , Impresión Molecular , Polímeros/química , Dióxido de Silicio/química , Espectrometría de Fluorescencia , Espectrofotometría UltravioletaRESUMEN
Photodynamic therapy (PDT) has attracted extensive attention in the clinical treatment of malignant tumor. However, the acidic and hypoxic conditions of the tumor microenvironment (TME) limit the further application of PDT in the clinic. Herein, we fabricate a new nanoplatformâHPDA@MnO2@Ce6/DOX@PEG-RGD (HPMRCD)âby means of coating hollow polydopamine nanoparticles (HPDA) with manganese dioxide (MnO2), which is modified by cyclic RGD functionalized poly(ethylene glycol) (PEG) and further co-loaded with a photosensitizer, Chlorin e6 (Ce6), and a chemotherapy drug, doxorubicin (DOX). This nanoplatform could be enriched in tumor tissues, then instantly dissociated under an acidic and H2O2-rich TME. The dual-responsive release of Mn2+ ions and oxygen (O2) can relieve tumor hypoxia, which can be used as a magnetic resonance contrast agent and the latter can enhance the PDT effect. Furthermore, the degradation of HPMRCD leads to an efficient loaded therapeutic molecule release, thus yielding a potential therapy to enhance tumor suppression by adopting the combined chemo-photodynamic therapy.
Asunto(s)
Antibióticos Antineoplásicos/farmacología , Materiales Biomiméticos/farmacología , Doxorrubicina/farmacología , Nanopartículas/química , Oxígeno/farmacología , Fotoquimioterapia , Hipoxia Tumoral/efectos de los fármacos , Animales , Antibióticos Antineoplásicos/química , Apoptosis/efectos de los fármacos , Materiales Biomiméticos/síntesis química , Materiales Biomiméticos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/química , Liberación de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Indoles/química , Indoles/farmacología , Compuestos de Manganeso/química , Compuestos de Manganeso/farmacología , Ensayo de Materiales , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Óxidos/química , Óxidos/farmacología , Oxígeno/química , Tamaño de la Partícula , Polímeros/química , Polímeros/farmacología , PorosidadRESUMEN
Immunoregulation represents a booming field of biomaterial design. The unique physical and chemical properties of biomaterials offer tremendous opportunities for development. Each of their parameters exerts immunogenic effects at the immune system, cellular, and molecular levels. Herein, the perspective summarizes the interaction of biomaterials with immune cells and the underlying mechanisms to control immunoregulation in a top-down manner, providing solid inspiration for biomedical applications of immunologically effective biomaterials.