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1.
Nature ; 629(8014): 1041-1046, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38720078

RESUMO

Electrocaloric1,2 and electrostrictive3,4 effects concurrently exist in dielectric materials. Combining these two effects could achieve the lightweight, compact localized thermal management that is promised by electrocaloric refrigeration5. Despite a handful of numerical models and schematic presentations6,7, current electrocaloric refrigerators still rely on external accessories to drive the working bodies8-10 and hence result in a low device-level cooling power density and coefficient of performance (COP). Here we report an electrocaloric thin-film device that uses the electro-thermomechanical synergy provided by polymeric ferroelectrics. Under one-time a.c. electric stimulation, the device is thermally and mechanically cycled by the working body itself, resulting in an external-driver-free, self-cycling, soft refrigerator. The prototype offers a directly measured cooling power density of 6.5 W g-1 and a peak COP exceeding 58 under a zero temperature span. Being merely a 30-µm-thick polymer film, the device achieved a COP close to 24 under a 4 K temperature span in an open ambient environment (32% thermodynamic efficiency). Compared with passive cooling, the thin-film refrigerator could immediately induce an additional 17.5 K temperature drop against an electronic chip. The soft, polymeric refrigerator can sense, actuate and pump heat to provide automatic localized thermal management.


Assuntos
Polímeros , Refrigeração , Termodinâmica , Refrigeração/instrumentação , Polímeros/química , Temperatura Baixa , Eletricidade , Desenho de Equipamento , Estimulação Elétrica , Temperatura
2.
Nature ; 631(8022): 884-890, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39020178

RESUMO

Plastic production reached 400 million tons in 2022 (ref. 1), with packaging and single-use plastics accounting for a substantial amount of this2. The resulting waste ends up in landfills, incineration or the environment, contributing to environmental pollution3. Shifting to biodegradable and compostable plastics is increasingly being considered as an efficient waste-management alternative4. Although polylactide (PLA) is the most widely used biosourced polymer5, its biodegradation rate under home-compost and soil conditions remains low6-8. Here we present a PLA-based plastic in which an optimized enzyme is embedded to ensure rapid biodegradation and compostability at room temperature, using a scalable industrial process. First, an 80-fold activity enhancement was achieved through structure-based rational engineering of a new hyperthermostable PLA hydrolase. Second, the enzyme was uniformly dispersed within the PLA matrix by means of a masterbatch-based melt extrusion process. The liquid enzyme formulation was incorporated in polycaprolactone, a low-melting-temperature polymer, through melt extrusion at 70 °C, forming an 'enzymated' polycaprolactone masterbatch. Masterbatch pellets were integrated into PLA by melt extrusion at 160 °C, producing an enzymated PLA film (0.02% w/w enzyme) that fully disintegrated under home-compost conditions within 20-24 weeks, meeting home-composting standards. The mechanical and degradation properties of the enzymated film were compatible with industrial packaging applications, and they remained intact during long-term storage. This innovative material not only opens new avenues for composters and biomethane production but also provides a feasible industrial solution for PLA degradation.


Assuntos
Plásticos Biodegradáveis , Biodegradação Ambiental , Enzimas Imobilizadas , Hidrolases , Poliésteres , Engenharia de Proteínas , Plásticos Biodegradáveis/química , Plásticos Biodegradáveis/metabolismo , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Hidrolases/metabolismo , Hidrolases/química , Poliésteres/química , Poliésteres/metabolismo , Solo/química , Temperatura , Estabilidade Enzimática , Compostagem
3.
Nat Chem Biol ; 20(10): 1380-1386, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38969863

RESUMO

Synthetic cells containing genetic programs and protein expression machinery are increasingly recognized as powerful counterparts to engineered living cells in the context of biotechnology, therapeutics and cellular modelling. So far, genetic regulation of synthetic cell activity has been largely confined to chemical stimuli; to unlock their potential in applied settings, engineering stimuli-responsive synthetic cells under genetic regulation is imperative. Here we report the development of temperature-sensitive synthetic cells that control protein production by exploiting heat-responsive mRNA elements. This is achieved by combining RNA thermometer technology, cell-free protein expression and vesicle-based synthetic cell design to create cell-sized capsules able to initiate synthesis of both soluble proteins and membrane proteins at defined temperatures. We show that the latter allows for temperature-controlled cargo release phenomena with potential implications for biomedicine. Platforms like the one presented here can pave the way for customizable, genetically programmed synthetic cells under thermal control to be used in biotechnology.


Assuntos
Células Artificiais , Biossíntese de Proteínas , Células Artificiais/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Temperatura , Temperatura Alta , Escherichia coli/genética , Escherichia coli/metabolismo
4.
Nature ; 583(7815): 242-248, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32641817

RESUMO

Enhanced silicate rock weathering (ERW), deployable with croplands, has potential use for atmospheric carbon dioxide (CO2) removal (CDR), which is now necessary to mitigate anthropogenic climate change1. ERW also has possible co-benefits for improved food and soil security, and reduced ocean acidification2-4. Here we use an integrated performance modelling approach to make an initial techno-economic assessment for 2050, quantifying how CDR potential and costs vary among nations in relation to business-as-usual energy policies and policies consistent with limiting future warming to 2 degrees Celsius5. China, India, the USA and Brazil have great potential to help achieve average global CDR goals of 0.5 to 2 gigatonnes of carbon dioxide (CO2) per year with extraction costs of approximately US$80-180 per tonne of CO2. These goals and costs are robust, regardless of future energy policies. Deployment within existing croplands offers opportunities to align agriculture and climate policy. However, success will depend upon overcoming political and social inertia to develop regulatory and incentive frameworks. We discuss the challenges and opportunities of ERW deployment, including the potential for excess industrial silicate materials (basalt mine overburden, concrete, and iron and steel slag) to obviate the need for new mining, as well as uncertainties in soil weathering rates and land-ocean transfer of weathered products.


Assuntos
Agricultura , Dióxido de Carbono/isolamento & purificação , Produtos Agrícolas , Sedimentos Geológicos/química , Aquecimento Global/prevenção & controle , Objetivos , Silicatos/química , Atmosfera/química , Brasil , China , Política Ambiental/economia , Política Ambiental/legislação & jurisprudência , Aquecimento Global/economia , Índia , Ferro/isolamento & purificação , Mineração , Política , Probabilidade , Silicatos/isolamento & purificação , Aço/isolamento & purificação , Temperatura , Fatores de Tempo , Estados Unidos
5.
J Neurosci ; 44(11)2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38316563

RESUMO

Cooling sensations arise inside the mouth during ingestive and homeostasis behaviors. Oral presence of cooling temperature engages the cold and menthol receptor TRPM8 (transient receptor potential melastatin 8) on trigeminal afferents. Yet, how TRPM8 influences brain and behavioral responses to oral temperature is undefined. Here we used in vivo neurophysiology to record action potentials stimulated by cooling and warming of oral tissues from trigeminal nucleus caudalis neurons in female and male wild-type and TRPM8 gene deficient mice. Using these lines, we also measured orobehavioral licking responses to cool and warm water in a novel, temperature-controlled fluid choice test. Capture of antidromic electrophysiological responses to thalamic stimulation identified that wild-type central trigeminal neurons showed diverse responses to oral cooling. Some neurons displayed relatively strong excitation to cold <10°C (COLD neurons) while others responded to only a segment of mild cool temperatures below 30°C (COOL neurons). Notably, TRPM8 deficient mice retained COLD-type but lacked COOL cells. This deficit impaired population responses to mild cooling temperatures below 30°C and allowed warmth-like (≥35°C) neural activity to pervade the normally innocuous cool temperature range, predicting TRPM8 deficient mice would show anomalously similar orobehavioral responses to warm and cool temperatures. Accordingly, TRPM8 deficient mice avoided both warm (35°C) and mild cool (≤30°C) water and sought colder temperatures in fluid licking tests, whereas control mice avoided warm but were indifferent to mild cool and colder water. Results imply TRPM8 input separates cool from warm temperature sensing and suggest other thermoreceptors also participate in oral cooling sensation.


Assuntos
Canais de Cátion TRPM , Camundongos , Masculino , Animais , Feminino , Canais de Cátion TRPM/genética , Temperatura Baixa , Neurônios , Temperatura , Sensação Térmica/fisiologia , Água
6.
Chem Rev ; 123(2): 736-810, 2023 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-36542491

RESUMO

Natural evolution has provided multicellular organisms with sophisticated functionalities and repair mechanisms for surviving and preserve their functions after an injury and/or infection. In this context, biological systems have inspired material scientists over decades to design and fabricate both self-healing polymeric materials and soft actuators with remarkable performance. The latter are capable of modifying their shape in response to environmental changes, such as temperature, pH, light, electrical/magnetic field, chemical additives, etc. In this review, we focus on the fusion of both types of materials, affording new systems with the potential to revolutionize almost every aspect of our modern life, from healthcare to environmental remediation and energy. The integration of stimuli-triggered self-healing properties into polymeric soft actuators endow environmental friendliness, cost-saving, enhanced safety, and lifespan of functional materials. We discuss the details of the most remarkable examples of self-healing soft actuators that display a macroscopic movement under specific stimuli. The discussion includes key experimental data, potential limitations, and mechanistic insights. Finally, we include a general table providing at first glance information about the nature of the external stimuli, conditions for self-healing and actuation, key information about the driving forces behind both phenomena, and the most important features of the achieved movement.


Assuntos
Hidrogéis , Polímeros , Polímeros/química , Hidrogéis/química , Temperatura
7.
Proc Natl Acad Sci U S A ; 119(13): e2116127119, 2022 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-35324328

RESUMO

SignificanceSoft materials can be toughened by creating dissipative mechanisms in stretchy matrixes. Yet using them over a wide range of temperatures requires dissipative mechanisms independent of stretch rate or temperature. We show that sacrificial covalent bonds in multiple network elastomers are most useful in toughening elastomers at high temperature and act synergistically with viscoelasticity at lower temperature. We do not attribute this toughening mechanism only to the scission of bonds during crack propagation but propose that the highly stretched network diluted in a stretchy matrix acts by simultaneously stiffening the elastomer and delaying the localization of bond scission and the propagation of a crack. Such a toughening mechanism has never been proposed for elastomers and should guide network design.


Assuntos
Elastômeros , Elastômeros/química , Temperatura
8.
Nano Lett ; 24(33): 10265-10274, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39116304

RESUMO

Artificial sensory afferent nerves that emulate receptor nanochannel perception and synaptic ionic information processing in chemical environments are highly desirable for bioelectronics. However, challenges persist in achieving life-like nanoscale conformal contact, agile multimodal sensing response, and synaptic feedback with ions. Here, a precisely tuned phase transition poly(N-isopropylacrylamide) (PNIPAM) hydrogel is introduced through the water molecule reservoir strategy. The resulting hydrogel with strongly cross-linked networks exhibits excellent mechanical performance (∼2000% elongation) and robust adhesive strength. Importantly, the hydrogel's enhanced ionic conductance and heterogeneous structure of the temperature-sensitive component enable highly sensitive strain information perception (GFmax = 7.94, response time ∼ 87 ms), temperature information perception (TCRmax = -1.974%/°C, response time ∼ 270 ms), and low energy consumption synaptic plasticity (42.2 fJ/spike). As a demonstration, a neuromorphic sensing-synaptic system is constructed integrating iontronic strain/temperature sensors with fiber synapses for real-time information sensing, discrimination, and feedback. This work holds enormous potential in bioinspired robotics and bioelectronics.


Assuntos
Resinas Acrílicas , Hidrogéis , Hidrogéis/química , Resinas Acrílicas/química , Temperatura , Sinapses/fisiologia , Adesivos/química
9.
Nano Lett ; 24(31): 9561-9568, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39042325

RESUMO

The perfect integration of microbubbles for efficient ultrasound imaging and nanocarriers for intelligent tumor-targeting delivery remains a challenge in precise tumor theranostics. Herein, we exquisitely fabricated laser-activated and targeted polymersomes (abbreviated as FIP-NPs) for simultaneously encapsulating the photosensitizer indocyanine green (ICG) and the phase change agent perfluorohexane (PFH). The formulated FIP-NPs were nanosize and effectively accumulated into tumors as observed by ICG fluorescence imaging. When the temperature rose above 56 °C, the encapsulated PFH transformed from liquid to gas and the FIP-NPs underwent balloon-like enlargement without structure destruction. Impressively, the enlarged FIP-NPs fused with adjacent polymersomes to form even larger microparticles. This temperature-responsive "nano-to-micro" transformation and fusion process was clearly demonstrated, and FIP-NPs showed greatly improved ultrasound signals. More importantly, FIP-NPs achieved dramatic antitumor efficacy through ICG-mediated phototherapy. Taken together, the novel polymersomes achieved excellent ultrasound/fluorescence dual imaging-guided tumor phototherapy, providing an optimistic candidate for the application of tumor theranostics.


Assuntos
Verde de Indocianina , Imagem Óptica , Fototerapia , Polímeros , Verde de Indocianina/química , Verde de Indocianina/uso terapêutico , Animais , Camundongos , Fototerapia/métodos , Humanos , Imagem Óptica/métodos , Polímeros/química , Nanopartículas/química , Nanopartículas/uso terapêutico , Fluorocarbonos/química , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Temperatura , Ultrassonografia/métodos , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Nanomedicina Teranóstica/métodos , Microbolhas/uso terapêutico
10.
Biophys J ; 123(12): 1542-1552, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38664965

RESUMO

Enzymatic recycling of plastic and especially of polyethylene terephthalate (PET) has shown great potential to reduce its negative impact on our society. PET hydrolases (PETases) have been optimized using rational design and machine learning, but the mechanistic details of the PET depolymerization process remain unclear. Belonging to the carboxylic-ester hydrolase family with a canonical Ser-His-Asp catalytic triad, their observed alkaline pH optimum is generally thought to be related to the protonation state of the catalytic His. Here, we explore this aspect in the context of LCCICCG, an optimized PETase, derived from the leaf-branch compost cutinase enzyme. We use NMR to identify the dominant tautomeric structure of the six histidines. Five show surprisingly low pKa values below 4.0, whereas the catalytic H242 in the active enzyme displays a pKa value that varies from 4.9 to 4.7 when temperatures increase from 30°C to 50°C. Whereas the hydrolytic activity of the enzyme toward a soluble substrate can be modeled by the corresponding protonation/deprotonation curve, an important discrepancy is found when the substrate is the solid plastic. This opens the way to further mechanistic understanding of the PETase activity and underscores the importance of studying the enzyme at the liquid-solid interface.


Assuntos
Polietilenotereftalatos , Concentração de Íons de Hidrogênio , Polietilenotereftalatos/química , Polietilenotereftalatos/metabolismo , Hidrolases de Éster Carboxílico/química , Hidrolases de Éster Carboxílico/metabolismo , Hidrólise , Temperatura , Modelos Moleculares
11.
J Am Chem Soc ; 146(31): 21664-21676, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39058398

RESUMO

Inspired by the unique functionalities of biomolecular membraneless organelles (MLOs) formed via liquid-liquid phase separation (LLPS) of intrinsically disordered proteins (IDPs) and nucleic acids, a great deal of effort has been devoted to devising phase-separated artificial subcellular dynamic compartments. These endeavors aim to unravel the molecular mechanism underlying the formation and intracellular delivery of susceptible macromolecular therapeutics. We report herein pyroglutamic acid (PGA)-based well-defined homopolymers featuring stimuli-tunable reversible self-coacervation ability. The polymer exhibits an upper critical solution temperature (UCST) transition in aqueous solutions and has the propensity to undergo cooling-induced LLPS, producing micrometer-sized liquid droplets. This phase separation phenomenon could be modulated by various factors, including polymer concentration, chain length, solution pH, and types and concentrations of different additives. These micrometer droplets are thermally reversible and encapsulate a wide variety of cargoes, including small hydrophobic fluorescent molecules, hydrophilic anticancer drugs, and fluorophore-labeled macromolecular proteins (bovine serum albumin and lysozyme). The payloads were released by exploiting the thermo/pH-mediated disassembly behavior of the coacervates, preserving the bioactivity of the sensitive therapeutics. This environmentally responsive, simple yet versatile artificial MLO model system will provide insights into the biomolecular nonionic condensates and pave the way for the de novo design of dynamic biomolecule depots.


Assuntos
Ligação de Hidrogênio , Humanos , Soroalbumina Bovina/química , Muramidase/química , Ácido Poliglutâmico/química , Ácido Poliglutâmico/análogos & derivados , Antineoplásicos/química , Concentração de Íons de Hidrogênio , Liberação Controlada de Fármacos , Temperatura , Polímeros/química , Interações Hidrofóbicas e Hidrofílicas
12.
Anal Chem ; 96(18): 7179-7186, 2024 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-38661266

RESUMO

This study uses real-time monitoring, at microsecond time scales, with a charge-sensing particle detector to investigate the evaporation and fission processes of methanol/micrometer-sized polystyrene beads (PS beads) droplets and bacterial particles droplets generated via electrospray ionization (ESI) under elevated temperatures. By incrementally raising capillary temperatures, the solvent, such as methanol on 0.75 µm PS beads, experiences partial evaporation. Further temperature increase induces fission, and methanol molecules continue to evaporate until PS ions are detected after this range. Similar partial evaporation is observed on 3 µm PS beads. However, the shorter period of the fission temperature range is necessary compared to 0.75 µm PS beads. For the spherical-shaped bacterium, Staphylococcus aureus, the desolvation process shows a similar fission period as compared to 0.75 µm PS beads. Comparably, the rod-shaped bacteria, Escherichia coli EC11303, and E. coli strain W have shorter fission periods than S. aureus. This research provides insights into the evaporation and fission mechanisms of ESI droplets containing different sizes and shapes of micrometer-sized particles, contributing to a better understanding of gaseous macroion formation.


Assuntos
Escherichia coli , Poliestirenos , Espectrometria de Massas por Ionização por Electrospray , Staphylococcus aureus , Poliestirenos/química , Escherichia coli/química , Tamanho da Partícula , Temperatura , Volatilização , Metanol/química , Microesferas
13.
Anal Chem ; 96(23): 9370-9378, 2024 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-38683892

RESUMO

The development of sensors for detection of biomarkers exhibits an exciting potential in diagnosis of diseases. Herein, we propose a novel electrochemical sensing strategy for label-free dual-biomarker detection, which is based on the combination of stimulus-responsive molecularly imprinted polymer (MIP)-modified nanopores and a polymeric membrane chronopotentiometric sensor. The ion fluxes galvanostatically imposed on the sensing membrane surface can be blocked by the recognition reaction between the target biomarker in the sample solution and the stimulus-responsive MIP receptor in the nanopores, thus causing a potential change. By using two external stimuli (i.e., pH and temperature), the recognition abilities of the stimulus-responsive MIP receptor can be effectively modulated so that dual-biomarker label-free chronopotentiometric detection can be achieved. Using alpha fetoprotein (AFP) and prostate-specific antigen (PSA) as model biomarkers, the proposed sensor offers detection limits of 0.17 and 0.42 ng/mL for AFP and PSA, respectively.


Assuntos
Biomarcadores , Polímeros Molecularmente Impressos , Nanoporos , Antígeno Prostático Específico , alfa-Fetoproteínas , Antígeno Prostático Específico/análise , Polímeros Molecularmente Impressos/química , alfa-Fetoproteínas/análise , Humanos , Biomarcadores/análise , Limite de Detecção , Técnicas Eletroquímicas/métodos , Concentração de Íons de Hidrogênio , Técnicas Biossensoriais/métodos , Potenciometria/métodos , Polímeros/química , Impressão Molecular , Temperatura
14.
BMC Biotechnol ; 24(1): 22, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664752

RESUMO

BACKGROUND: The advancement of AAV vectors into clinical testing has accelerated rapidly over the past two decades. While many of the AAV vectors being utilized in clinical trials are derived from natural serotypes, engineered serotypes are progressing toward clinical translation due to their enhanced tissue tropism and immune evasive properties. However, novel AAV vectors require formulation and stability testing to determine optimal storage conditions prior to their use in a clinical setting. RESULTS: Here, we evaluated the thermal stability of AAV6.2FF, a rationally engineered capsid with strong tropism for lung and muscle, in two different buffer formulations; phosphate buffered saline (PBS), or PBS supplemented with 0.001% non-ionic surfactant Pluronic F68 (PF-68). Aliquots of AAV6.2FF vector encoding the firefly luciferase reporter gene (AAV6.2FF-ffLuc) were incubated at temperatures ranging from -20°C to 55°C for varying periods of time and the impact on infectivity and particle integrity evaluated. Additionally, the impact of several rounds of freeze-thaw treatments on the infectivity of AAV6.2FF was investigated. Vector infectivity was measured by quantifying firefly luciferase expression in HEK 293 cells and AAV particle integrity was measured by qPCR quantification of encapsidated viral DNA. CONCLUSIONS: Our data demonstrate that formulating AAV6.2FF in PBS containing 0.001% PF-68 leads to increased stability and particle integrity at temperatures between -20℃ to 21℃ and protection against the destructive effects of freeze-thaw. Finally, AAV6.2FF-GFP formulated in PBS supplemented with 0.001% PF-68 displayed higher transduction efficiency in vivo in murine lung epithelial cells following intranasal administration than vector buffered in PBS alone further demonstrating the beneficial properties of PF-68.


Assuntos
Dependovirus , Vetores Genéticos , Poloxâmero , Animais , Humanos , Células HEK293 , Poloxâmero/farmacologia , Poloxâmero/química , Camundongos , Dependovirus/genética , Vetores Genéticos/genética , Luciferases de Vaga-Lume/genética , Luciferases de Vaga-Lume/metabolismo , Temperatura , Genes Reporter
15.
Small ; 20(30): e2310072, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38470190

RESUMO

Flexible wearable sensors recently have made significant progress in human motion detection and health monitoring. However, most sensors still face challenges in terms of single detection targets, single application environments, and non-recyclability. Lipoic acid (LA) shows a great application prospect in soft materials due to its unique properties. Herein, ionic conducting elastomers (ICEs) based on polymerizable deep eutectic solvents consisting of LA and choline chloride are prepared. In addition to the good mechanical strength, high transparency, ionic conductivity, and self-healing efficiency, the ICEs exhibit swelling-strengthening behavior and enhanced adhesion strength in underwater environments due to the moisture-induced association of poly(LA) hydrophobic chains, thus making it possible for underwater sensing applications, such as underwater communication. As a strain sensor, it exhibits highly sensitive strain response with repeatability and durability, enabling the monitoring of both large and fine human motions, including joint movements, facial expressions, and pulse waves. Furthermore, due to the enhancement of ion mobility at higher temperatures, it also possesses excellent temperature-sensing performance. Notably, the ICEs can be fully recycled and reused as a new strain/temperature sensor through heating. This study provides a novel strategy for enhancing the mechanical strength of poly(LA) and the fabrication of multifunctional sensors.


Assuntos
Ácido Tióctico , Água , Dispositivos Eletrônicos Vestíveis , Ácido Tióctico/química , Água/química , Humanos , Temperatura , Elastômeros/química
16.
Small ; 20(31): e2312140, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38456378

RESUMO

Uncontrolled and excessive photothermal heating in photothermal therapy (PTT) inevitably causes thermal damage to surrounding normal tissues, severely limiting the universality and safety of PTT. To address this issue, an intelligent cooling thermal-responsive (ICTR) gel containing poly(N-isopropylacrylamide-co-acrylamide) (P(NIPAM-AM))microgel is applied onto the skin to realize intelligent PTT, which can avoid excessive heating and accidental injury. The high near-infrared (NIR) light transmittance (> 95%) of the ICTR gel ensures effective light delivery at low temperatures, while the refractive index of the P(NIPAM-AM) microgel increases remarkably when the temperature exceeds a predetermined threshold, resulting in progressively enhanced light scattering and weakened photothermal conversion. In animal studies, the negative feedback regulation of ICTR gel on light transmittance and photothermal heating allows the photothermal temperature in the lesion site to be stabilized within the effective therapeutic range (45 °C) while ensuring that the skin surface temperature does not exceed 35 °C. Compared with the severe skin thermal damage found in the histological staining of mice skin receiving conventional PTT, the mice skin receiving the ICTR gel-enabled intelligent PTT remains in good condition. This study establishes an intelligent and universal paradigm for PTT thermal regulation, which is of great significance for achieving safe and effective PTT.


Assuntos
Géis , Terapia Fototérmica , Animais , Terapia Fototérmica/métodos , Géis/química , Camundongos , Temperatura , Pele/patologia , Resinas Acrílicas/química , Fototerapia/métodos
17.
Small ; 20(32): e2311166, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38693075

RESUMO

Thermoresponsive nanogels (tNGs) are promising candidates for dermal drug delivery. However, poor incorporation of hydrophobic drugs into hydrophilic tNGs limits the therapeutic efficiency. To address this challenge, ß-cyclodextrins (ß-CD) are functionalized by hyperbranched polyglycerol serving as crosslinkers (hPG-ßCD) to fabricate ßCD-tNGs. This novel construct exhibits augmented encapsulation of hydrophobic drugs, shows the appropriate thermal response to dermal administration, and enhances the dermal penetration of payloads. The structural influences on the encapsulation capacity of ßCD-tNGs for hydrophobic drugs are analyzed, while concurrently retaining their efficacy as skin penetration enhancers. Various synthetic parameters are considered, encompassing the acrylation degree and molecular weight of hPG-ßCD, as well as the monomer composition of ßCD-tNGs. The outcome reveals that ßCD-tNGs substantially enhance the aqueous solubility of Nile Red elevating to 120 µg mL-1 and augmenting its dermal penetration up to 3.33 µg cm-2. Notably, the acrylation degree of hPG-ßCD plays a significant role in dermal drug penetration, primarily attributed to the impact on the rigidity and hydrophilicity of ßCD-tNGs. Taken together, the introduction of the functionalized ß-CD as the crosslinker in tNGs presents a novel avenue to enhance the efficacy of hydrophobic drugs in dermatological applications, thereby offering promising opportunities for boosted therapeutic outcomes.


Assuntos
Glicerol , Interações Hidrofóbicas e Hidrofílicas , Nanogéis , Polímeros , beta-Ciclodextrinas , beta-Ciclodextrinas/química , Glicerol/química , Nanogéis/química , Polímeros/química , Animais , Polietilenoimina/química , Reagentes de Ligações Cruzadas/química , Temperatura , Absorção Cutânea , Pele/metabolismo , Polietilenoglicóis/química , Oxazinas
18.
Small ; 20(31): e2310340, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38456789

RESUMO

Chondrosarcoma(CS), a prevalent primary malignant bone tumor, frequently exhibits chemotherapy resistance attributed to upregulated anti-apoptosis pathways such as the Bcl-2 family. In this manuscript, a new strategy is presented to augment chemosensitivity and mitigate systemic toxicity by harnessing a nano-enabled drug delivery hydrogel platform. The platform utilizes "PLGA-PEG-PLGA", an amphiphilic triblock copolymer combining hydrophilic polyethylene glycol (PEG) and hydrophobic polylactide glycolide (PLGA) blocks, renowned for its properties conducive to crafting a biodegradable, temperature-sensitive hydrogel. This platform is tailored to encapsulate a ratiometrically designed dual-loaded liposomes containing a first-line chemo option for CS, Doxorubicin (Dox), plus a calculated amount of small molecule inhibitor for anti-apoptotic Bcl-2 pathway, ABT-737. In vitro and in vivo evaluations demonstrate successful Bcl-2 suppression, resulting in the restoration of Dox sensitivity, evident through impeded tumor growth and amplified necrosis rates at the tumor site. This delivery system showcases remarkable thermal responsiveness, injectability, and biodegradability, all finely aligned with the clinical demands of CS treatment. Collectively, this study introduces a transformative avenue for tackling drug resistance in CS chemotherapy, offering significant clinical potential.


Assuntos
Condrossarcoma , Doxorrubicina , Sistemas de Liberação de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Hidrogéis , Nanocompostos , Condrossarcoma/tratamento farmacológico , Condrossarcoma/patologia , Condrossarcoma/metabolismo , Nanocompostos/química , Animais , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Hidrogéis/química , Doxorrubicina/farmacologia , Doxorrubicina/química , Doxorrubicina/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Humanos , Linhagem Celular Tumoral , Temperatura , Polietilenoglicóis/química , Camundongos
19.
Appl Environ Microbiol ; 90(3): e0224223, 2024 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-38358247

RESUMO

The extensive accumulation of polyethylene terephthalate (PET) has become a critical environmental issue. PET hydrolases can break down PET into its building blocks. Recently, we identified a glacial PET hydrolase GlacPETase sharing less than 31% amino acid identity with any known PET hydrolases. In this study, the crystal structure of GlacPETase was determined at 1.8 Å resolution, revealing unique structural features including a distinctive N-terminal disulfide bond and a specific salt bridge network. Site-directed mutagenesis demonstrated that the disruption of the N-terminal disulfide bond did not reduce GlacPETase's thermostability or its catalytic activity on PET. However, mutations in the salt bridges resulted in changes in melting temperature ranging from -8°C to +2°C and the activity on PET ranging from 17.5% to 145.5% compared to the wild type. Molecular dynamics simulations revealed that these salt bridges stabilized the GlacPETase's structure by maintaining their surrounding structure. Phylogenetic analysis indicated that GlacPETase represented a distinct branch within PET hydrolases-like proteins, with the salt bridges and disulfide bonds in this branch being relatively conserved. This research contributed to the improvement of our comprehension of the structural mechanisms that dictate the thermostability of PET hydrolases, highlighting the diverse characteristics and adaptability observed within PET hydrolases.IMPORTANCEThe pervasive problem of polyethylene terephthalate (PET) pollution in various terrestrial and marine environments is widely acknowledged and continues to escalate. PET hydrolases, such as GlacPETase in this study, offered a solution for breaking down PET. Its unique origin and less than 31% identity with any known PET hydrolases have driven us to resolve its structure. Here, we report the correlation between its unique structure and biochemical properties, focusing on an N-terminal disulfide bond and specific salt bridges. Through site-directed mutagenesis experiments and molecular dynamics simulations, the roles of the N-terminal disulfide bond and salt bridges were elucidated in GlacPETase. This research enhanced our understanding of the role of salt bridges in the thermostability of PET hydrolases, providing a valuable reference for the future engineering of PET hydrolases.


Assuntos
Hidrolases , Polietilenotereftalatos , Polietilenotereftalatos/metabolismo , Filogenia , Estabilidade Enzimática , Hidrolases/metabolismo , Dissulfetos , Temperatura
20.
Appl Environ Microbiol ; 90(2): e0201623, 2024 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-38214515

RESUMO

Global warming has led to a high incidence of extreme heat events, and the frequent occurrence of extreme heat events has had extensive and far-reaching impacts on wetland ecosystems. The widespread distribution of plastics in the environment, including polyethylene (PE), polylactic acid (PLA), and tire particles (TPs), has caused various environmental problems. Here, high-throughput sequencing techniques and metabolomics were used for the first time to investigate the effects of three popular microplastic types: PE, PLA, and TP, on the sediment microbiome and the metabolome at both temperatures. The microplastics were incorporated into the sediment at a concentration of 3% by weight of the dry sediment (wt/wt), to reflect environmentally relevant conditions. Sediment enzymatic activity and physicochemical properties were co-regulated by both temperatures and microplastics producing significant differences compared to controls. PE and PLA particles inhibited bacterial diversity at low temperatures and promoted bacterial diversity at high temperatures, and TP particles promoted both at both temperatures. For bacterial richness, only PLA showed inhibition at low temperature; all other treatments showed promotion. PE, PLA, and TP microplastics changed the community structure of sediment bacteria, forming two clusters at low and high temperatures. Furthermore, PE, PLA, and TP changed the sediment metabolic profiles, producing differential metabolites such as lipids and molecules, organic heterocyclic compounds, and organic acids and their derivatives, especially TP had the most significant effect. These findings contribute to a more comprehensive understanding of the potential impact of microplastic contamination.IMPORTANCEIn this study, we added 3% (wt/wt) microplastic particles, including polyethylene, polylactic acid, and tire particles, to natural sediments under simulated laboratory conditions. Subsequently, we simulated the sediment microbial and ecosystem responses under different temperature conditions by incubating them for 60 days at 15°C and 35°C, respectively. After synthesizing these results, our study strongly suggests that the presence of microplastics in sediment ecosystems and exposure under different temperature conditions may have profound effects on soil microbial communities, enzyme activities, and metabolite profiles. This is important for understanding the potential hazards of microplastic contamination on terrestrial ecosystems and for developing relevant environmental management strategies.


Assuntos
Microbiota , Poluentes Químicos da Água , Plásticos , Microplásticos/química , Microplásticos/farmacologia , Polietileno/análise , Polietileno/farmacologia , Ecossistema , Temperatura , Poluentes Químicos da Água/análise , Sedimentos Geológicos/microbiologia , Poliésteres , Metaboloma , Monitoramento Ambiental
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