RESUMEN
This work details a novel application of MgAl-LDH nanoflowers, applied in the fabrication of humidity sensors using quartz crystal microbalance (QCM). An oscillating circuit approach has been utilized to thoroughly investigate the humidity detection characteristics of QCM sensors that are fabricated using MgAl-LDH nanoflowers. The examination encompassed various parameters such as the sensors' response, humidity hysteresis, repeatability, and stability. Experimental results clearly indicate that these MgAl-LDH nanoflower-based QCM sensors exhibit a distinct logarithmic frequency response to varying moisture levels. Notably, the sensitivity of the sensors is intricately tied to the amount of MgAl-LDH nanoflowers utilized during the deposition process. Moreover, these sensors maintain remarkable stability across a wide humidity range spanning from 11% to 97% RH. Additionally, the MgAl-LDH nanoflower-based QCM sensors possess minimal humidity hysteresis and display swift dynamic response and recovery periods, further highlighting their potential for humidity detection applications.
RESUMEN
Combining the phosphonic acid group with the sulfonic acid group in PEMs has been shown to be an effective strategy for improving the fuel cell performance. However, the interplay of two different ionic groups and the resulting effect on the membrane properties have not been fully elucidated. Here, we used classical molecular dynamics simulation to investigate the morphologies, transport properties and effects of ionic groups in a novel perfluorinated PEM containing two ionic groups (PFSA-PFPA) in comparison to the corresponding homopolymers. Phase separations between hydrophilic and hydrophobic domains are confirmed in these PEMs and result from the evolution of water clusters formed around the ionic groups. The combination of both ionic groups brings a complicated morphological feature in PFSA-PFPA, with near-cylindrical aqueous domains of large length scales interconnected by tortuous domains of small sizes. And we found that the self-diffusion coefficients of water molecules are strongly related to morphologies, with the water transport in PFSA-PFPA lying between two analogous homopolymers. At the molecular level, we found that the sulfonic and phosphonic acid groups have distinct effects on the coordination behaviors and the dynamics of water molecules and hydronium ions. Strong electrostatic interactions lead to compact coordination structures and sluggish dynamics of hydronium ions around phosphonic acid groups, which determine the morphological evolution and transport properties in PFSA-PFPA. Our study affords insights into the relationship between molecular characteristics and transport properties bridged by phase-separated morphologies in a novel PEM containing both sulfonic acid and phosphonic acid groups, which deepens the understanding of the interplay between two ionic groups and may inspire the rational design of high-performance PEMs.
RESUMEN
The combination of anti-rheumatoid arthritis (RA) drugs methotrexate (MTX) and baricitinib (BTN) has been reported to improve RA treatment efficacy. However, study on the strategy of combination is elusive when considering the benefit of the synergy between MTX and BTN. In this study, we found that the N-heterocyclic rings in the MTX and BTN offer hydrogen bonds and π-π stacking interactions, driving the formation of exquisite vesicular morphology of nanovesicles, denoted as MB NVs. The MB NVs with the MTX/BTN weight ratio of 2:1, MB NVs (2:1), showed an improved anti-RA effect through the synergy between the anti-inflammatory and antiproliferative responses. This work presents that the intermolecular interactions between drug molecules could mediate the coassembly behavior into nanomedicine as well as the therapy synergy both in vitro and in vivo, which may provide further understanding on the rational design of combination nanomedicine for therapeutic purposes.
Asunto(s)
Antirreumáticos , Artritis Reumatoide , Azetidinas , Purinas , Pirazoles , Sulfonamidas , Humanos , Metotrexato/farmacología , Metotrexato/uso terapéutico , Antirreumáticos/farmacología , Antirreumáticos/uso terapéutico , Nanomedicina , Artritis Reumatoide/tratamiento farmacológico , Resultado del Tratamiento , Quimioterapia CombinadaRESUMEN
Industry 4.0, boosting the integration of sophisticated computational and manufacturing technologies, has profoundly reshaped the way to deal with market dynamics. It increases the capabilities of multi-stakeholders to engage in value co-creation for product innovation. Nonetheless, it also poses challenges to operation efficiency, i.e., surged requirements meeting expedited delivery times, in account of stakeholders' diverse backgrounds and goals. To respond, by applying the technology of Digital Twin (DT), this study proposes an Augmented Reality-assisted Cloud Additive Manufacturing (AR-CAM) framework, establishing a sophisticated cyber-physical interface to cater to various coordinating interactions. By this means, it attempts to give a consistent understanding to multi-background stakeholders. A case study involving the fabrication of a speed rear derailleur is applied, thereby underscoring the validity of the AR-CAM framework.
RESUMEN
With the emergence of Artificial Intelligence (AI) 2.0, computers are now equipped with new creative capabilities and are playing an increasingly significant role in design. The use of AI augmentation has the potential to enhance design performance, however, there is limited research on the acceptance of AI-augmented design. The research gap under consideration in this study is addressed by presenting an acceptance model designed for AI-augmented design. This model integrates a range of variables including perceived privacy risk, enjoyment, perceived value, perceived usefulness, perceived ease of use, perceived behavioral control, social influence, and behavioral intention. The proposed model was validated through a questionnaire survey of 249 designers in China. The results reveal that enjoyment, perceived value, perceived ease of use, perceived behavioral control, and social influence have a significant positive impact on users' intention to use AI-augmented design, while perceived privacy risk has a significant negative impact. Perceived value was found to mediate the relationship between enjoyment and behavioral intention, while perceived behavioral control play a mediation role in the relationship between social influence and behavioral intention. In conclusion, this study highlights the variables that influence the acceptance of AI-augmented design and provides valuable insights into the potential benefits and drawbacks of integrating AI technologies in design. The proposed acceptance model serves as a framework for future research in this area and can guide the development of more user-friendly and effective AI-augmented design tools and technologies.
RESUMEN
Gas sensors with exceptional sensitivity and selectivity are vital in the real-time surveillance of noxious and harmful gases. Despite this, traditional gas sensing materials still face a number of challenges, such as poor selectivity, insufficient detection limits, and short lifespan. Metal oxides, which are derived from metal-organic framework materials (MOFs), have been widely used in the field of gas sensors because they have a high surface area and large pore volume. Incorporating metal oxides derived from MOFs into gas sensors can improve their sensitivity and selectivity, thus opening up new possibilities for the development of innovative, high-performance gas sensors. This article examines the gas sensing process of metal oxide semiconductors (MOS), evaluates the advances made in the research of different structures of MOF-derived metal oxides in resistive gas sensors, and provides information on their potential applications and future advancements.
RESUMEN
BACKGROUND: The aberrant expression of serpin family E member 1 (SERPINE1) is associated with carcinogenesis. This study assessed the alteration of SERPINE1 expression for an association with gastric adenocarcinoma prognosis. METHODS: The Cancer Genome Atlas (TCGA) dataset was applied to investigate the impact of SERPINE1 expression on the survival of patients afflicted with gastric cancer. Subsequently, 136 samples from the Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University were subjected to qRT-PCR and Western blot to validate the expression level of SERPINE1 between tumor and adjacent normal tissues. The correlation between the expression of SERPINE1 with the clinicopathological features in TCGA patients was analyzed using Wilcoxon signed-rank and logistic regression tests. The potential molecular mechanism associated with SERPINE1 expression in gastric cancer were confirmed using gene set enrichment analysis (GSEA). RESULTS: The TCGA data showed that SERPINE1 was overexpressed in tumor tissues compared to normal mucosae and associated with the tumor T stage and pathological grade. SERPINE1 overexpression was associated with the poor overall survival (OS) of patients. The findings were confirmed with 136 patients, that is, SERPINE1 expression was associated with poor OS (hazard ratio (HR): 1.82; 95% confidence interval (CI): 0.84-1.83; p = 0.012)) as an independent predictor (HR: 2.11, 95% CI: 0.81-2.34; p = 0.009). The resulting data were further processed by GSEA showed that SERPINE1 overexpression was associated with the activation of EPITHELIAL_MESENCHYMAL_TRANSITION, TNFA_SIGNALING_VIA_NFKB, INFLAMMATORY_RESPONSE, ANGIOGENESIS, and HYPOXIA. CONCLUSIONS: SERPINE1 overexpression is associated with a poor gastric cancer prognosis.
RESUMEN
BACKGROUND AND OBJECTIVE: Enhanced recovery after surgery (ERAS) is a multidisciplinary,and evidence-based perioperative care method. It is effective in shortening hospital stays and improving clinical outcomes. However, the application of ERAS in craniotomy lacks reliable evidence. The purpose of this study is to investigate the efficacy and safety of ERAS in craniotomy. METHODS: Studies of ERAS in craniotomy were systematically searched in PubMed, Embase, Cochrane, and Web of Science. Primary outcomes (total hospital stay and postoperative hospital stay, hospitalization cost, percent of patients with moderate to severe pain) and secondary outcomes (readmission rate and incidence of complication) were compared between ERAS and traditional perioperative care. RESULT: Of the 10 studies included in this meta-analysis, 6 were randomized-controlled trials (RCTs), 3 were cohort studies, and 1 was non-RCT. A total of 1275 patients were included, with 648 in the ERAS group and 627 in the control group. Compared with the control group, the ERAS group had a significantly shortened total length of stay (LOS) (MD = -2.437, 95% CI: -3.616, -1.077, P = 0.001) and postoperative LOS, reduced hospitalization cost (SMD = -0.631, 95% CI: -0.893, -0.369, P = 0.001), and lower percent of patients with moderate to severe pain. There was no significant difference in readmission rate between the two groups. Though, the ERAS group had a significantly lower risk of pneumonia than the control group. CONCLUSION: ERAS is safe and effective for craniotomy as it shortens total and postoperative LOS, reduces hospitalization costs, decreases the percent of patients with moderate to severe pain.
Asunto(s)
Recuperación Mejorada Después de la Cirugía , Humanos , Atención Perioperativa/efectos adversos , Atención Perioperativa/métodos , Estudios de Cohortes , Craneotomía , Dolor/complicaciones , Complicaciones Posoperatorias/epidemiologíaRESUMEN
Hierarchical self-assembly of synthetic polymers in solution represents one of the sophisticated strategies to replicate the natural superstructures which lay the basis for their superb functions. However, it is still quite challenging to increase the degree of complexity of the as-prepared assemblies, especially in a large scale. Liquid-liquid phase separation (LLPS) widely exists in cells and is assumed to be responsible for the formation of many cellular organelles without membranes. Herein, through integrating LLPS with the polymerization-induced self-assembly (PISA), a coacervate-assisted PISA (CAPISA) methodology to realize the one-pot and scalable preparation of hierarchical bishell capsules (BCs) from nanosheets with ultrathin lamellae phase (sub-5 nm), microflakes, unishell capsules to final BCs in a bottom-up sequence is presented. Both the self-assembled structure and the dynamic formation process of BCs have been disclosed. Since CAPISA has combined the advantages of coacervates, click chemistry, interfacial reaction and PISA, it is believed that it will become a promising option to fabricate biomimetic polymer materials with higher structural complexity and more sophisticated functions.
RESUMEN
Supramolecular self-assembly is a promising strategy for stabilizing the photo-sensitive components in photocatalysis. However, the underlying correlation between the enhanced photostability and supramolecular structure at the molecular level has not yet been fully understood. Herein, we develop a biomimetic vesicular membrane-based polyporphyrin photocatalyst exhibiting excellent photocatalytic stability with at least activity time of 240â h in hydrogen generation. Time-domain ab initio modelling together with transient absorption spectroscopy, visual frontier orbitals and Gibbs free energy calculation disclose that the ordered aggregation of porphyrin units in the vesicle membrane facilitates "hot" electron relaxation and the rapid dissipation of photo-generated charges, thereby contributing to the longevity. This work deepens the molecular-level understanding on photostability and photocatalytic mechanism of supramolecular photocatalysts.
RESUMEN
Inspired by carbon monoxide dehydrogenase (CODH), mimicking its inner and outer spheres is a promising strategy in CO2 reduction catalyst design. However, artificial CODH-like catalysts are generally limited to the inner sphere effect and only applicable in organic solvents or for electrocatalysis. Herein, an aqueous CODH mimic with both inner and outer spheres for photocatalysis is reported. In this polymeric unimolecular catalyst, the inner sphere is composed of cobalt porphyrin with four appended amido groups and the outer sphere consists of four poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) arms. Upon visible light irradiation (λ >420â nm), the as-prepared catalyst exhibits a turnover number (TONCO ) of 1731.2 in the reduction of CO2 into CO, which is comparable to most reported molecular catalysts in aqueous solution. The mechanism studies indicate that, in this water-dispersible and structurally well-defined CODH mimic, the cobalt porphyrin core serves as the catalysis center and the amido groups function as hydrogen-bonding pillars helping to stabilize the CO2 adduct intermediate, whereas the PDMAEMA shell renders both water solubility and a CO2 reservoir through reversibly capturing of CO2 . The present work has clarified the significance of coordination sphere effects for improving the aqueous photocatalytic CO2 reduction performance of CODH mimics.
Asunto(s)
Imitación Molecular , Soluciones , Catálisis , Oxidación-Reducción , Dióxido de Carbono/química , MicelasRESUMEN
Aging is an important risk factor for neurodegenerative diseases. The activation of α7 nicotinic acetylcholine receptor (α7nAChR) is involved in inflammation and cognition, but the specific role it plays in aging remains unknown. This study aimed to investigate the anti-aging effect of the activation of α7nAChR on aging rats and BV2 cells induced by D-galactose, as well as its potential mechanism. D-galactose induced an increase in the SA-ß-Gal positive cells, expression of p16 and p21 in vivo and in vitro. α7nAChR selective agonist PNU282987 decreased levels of pro-inflammatory factors, MDA, and Aß, enhanced SOD activity and levels of anti-inflammatory factor (IL10) in vivo. PNU282987 enhanced the expression of Arg1, decreased the expression of iNOS, IL1ß and TNFα in vitro. PNU282987 upregulated the levels of α7nAChR, Nrf2 and HO-1 in vivo and in vitro. The results of Morris water maze and novel object recognition tests showed that PNU282987 improved cognitive impairment in aging rats. Furthermore, α7nAChR selective inhibitor methyllycaconitine (MLA) results were opposite with PNU282987. PNU282987 improves cognitive impairment through inhibiting oxidative stress and neuroinflammation in D-galactose induced aging via regulating the α7nAChR/Nrf2/HO-1 signaling pathway. Therefore, targeting the α7nAChR may be a viable therapeutic approach for anti-inflammaging and neurodegenerative diseases.
Asunto(s)
Disfunción Cognitiva , Receptor Nicotínico de Acetilcolina alfa 7 , Ratas , Animales , Receptor Nicotínico de Acetilcolina alfa 7/agonistas , Receptor Nicotínico de Acetilcolina alfa 7/metabolismo , Galactosa/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Enfermedades Neuroinflamatorias , Estrés Oxidativo , Envejecimiento , Transducción de Señal , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/inducido químicamenteRESUMEN
For capacitive energy storage at elevated temperatures1-4, dielectric polymers are required to integrate low electrical conduction with high thermal conductivity. The coexistence of these seemingly contradictory properties remains a persistent challenge for existing polymers. We describe here a class of ladderphane copolymers exhibiting more than one order of magnitude lower electrical conductivity than the existing polymers at high electric fields and elevated temperatures. Consequently, the ladderphane copolymer possesses a discharged energy density of 5.34 J cm-3 with a charge-discharge efficiency of 90% at 200 °C, outperforming the existing dielectric polymers and composites. The ladderphane copolymers self-assemble into highly ordered arrays by π-π stacking interactions5,6, thus giving rise to an intrinsic through-plane thermal conductivity of 1.96 ± 0.06 W m-1 K-1. The high thermal conductivity of the copolymer film permits efficient Joule heat dissipation and, accordingly, excellent cyclic stability at elevated temperatures and high electric fields. The demonstration of the breakdown self-healing ability of the copolymer further suggests the promise of the ladderphane structures for high-energy-density polymer capacitors operating under extreme conditions.
RESUMEN
BACKGROUND: Alcohol abuse triggers neuroinflammation, leading to neuronal damage and further memory and cognitive impairment. Few satisfactory advances have been made in the management of alcoholic central nervous impairment. Therefore, novel and more practical treatment options are urgently needed. Butyrate, a crucial metabolite of short-chain fatty acids (SCFAs), has been increasingly demonstrated to protect against numerous metabolic diseases. However, the impact of butyrate on chronic alcohol consumption-induced central nervous system (CNS) lesions remains unknown. METHODS: In this study, we assessed the possible effects and underlying mechanisms of butyrate on the attenuation of alcohol-induced CNS injury in mice. Firstly, sixty female C57BL/6 J mice were randomly divided into 4 groups: pair-fed (PF) group (PF/CON), alcohol-fed (AF) group (AF/CON), PF with sodium butyrate (NaB) group (PF/NaB) and AF with NaB group (AF/NaB). Each group was fed a modified Lieber-DeCarli liquid diet with or without alcohol. After six weeks of feeding, the mice were euthanized and the associated indicators were investigated. RESULTS: As indicated by the behavioral tests and brain morphology, dietary NaB administration significantly ameliorated aberrant behaviors, including locomotor hypoactivity, anxiety disorder, depressive behavior, impaired learning, spatial recognition memory, and effectively reduced chronic alcoholic central nervous system damage. To further understand the underlying mechanisms, microglia-mediated inflammation and the associated M1/M2 polarization were measured separately. Firstly, pro-inflammatory TNF-α, IL-1ß, and IL-6 in brain and peripheral blood circulation were decreased, but IL-10 were increased in the AF/NaB group compared with the AF/CON group. Consistently, the abnormal proportions of activated and resting microglial cells in the hippocampus and cortex regions after excessive alcohol consumption were significantly reduced with NaB treatment. Moreover, the rectification of microglia polarization (M1/M2) imbalance was found after NaB administration via binding GPR109A, up-regulating the expression of PPAR-γ and down-regulating TLR4/NF-κB activation. In addition to the direct suppression of neuroinflammation, intriguingly, dietary NaB intervention remarkably increased the levels of intestinal tight junction protein occludin and gut morphological barrier, attenuated the levels of serum lipopolysaccharide (LPS) and dysbiosis of gut microbiota, suggesting that NaB supplementation effectively improved the integrity and permeability of gut microecology. Finally, the neurotransmitters including differential Tryptophan (Trp) and Kynurenine (Kyn) were found with dietary NaB administration, which showed significantly altered and closely correlated with the gut microbiota composition, demonstrating the complex interactions in the microbiome-gut-brain axis involved in the efficacy of dietary NaB therapy for alcoholic CNS lesions. CONCLUSION: Dietary microbial metabolite butyrate supplementation ameliorates chronic alcoholic central nervous damage and improves related memory and cognitive functions through suppressing microglia-mediated neuroinflammation by GPR109A/PPAR-γ/TLR4-NF-κB signaling pathway and modulating microbiota-gut-brain axis.
Asunto(s)
Eje Cerebro-Intestino , Microglía , Ratones , Femenino , Animales , Enfermedades Neuroinflamatorias , FN-kappa B/farmacología , Receptor Toll-Like 4 , Receptores Activados del Proliferador del Peroxisoma , Ratones Endogámicos C57BL , Etanol/toxicidad , Ácido Butírico/farmacologíaRESUMEN
There is a growing conflict between building density and the comfort of the external environment in residential construction, especially in high-density cities in China. To address this conflict, a sensible building layout has to take both aspects into account. However, it is difficult for traditional planning approaches to produce a sensible building layout. This is partly due to the fact that an architect's subjective experiences are unreliable. On the other hand, the wind environment simulations of professional software are often time-consuming so that they are difficult to apply efficiently in practice. This study therefore focuses on the automatic generation of optimized high-density residential building layouts as well as the fast and accurate calculation of the corresponding wind environments. By combining the automatic optimization function of a genetic algorithm and the prediction function of a fully convolutional neural network, an intelligent planning method is proposed for producing optimal high-density residential building layouts in consideration of the local wind environment. To further verify its practicality and significance, a case study was carried out in the Yangtze River Delta region, China, through the automatic generation of a residential building layout, wind environment simulation, and a scheme comparison for optimization.
RESUMEN
Oxidative stress and neuroinflammation play crucial roles in aging. S-adenosylmethionine (SAM), a popular supplement, is a potential antioxidant and candidate therapy for depression. This study aimed to evaluate the neuroprotective effects of SAM on D-galactose-induced brain aging and explore its underlying mechanisms. Brain aging model was established with D-galactose (180 mg/kg/day) for 8 weeks. During the last 4 weeks, SAM (16 mg/kg) was co-administrated with D-galactose. Behavior tests were used to assess cognitive function and depression-like behaviors of rats. Results showed that cognitive impairment and depression-like behaviors were reversed by SAM. SAM reduced neuronal cell loss, increased brain-derived neurotrophic factor level in the hippocampus, inhibited amyloid-ß level and microglia activation, as well as pro-inflammatory factors levels in the hippocampus and serum. Further, SAM enhanced antioxidant capacity and attenuated cholinergic damage by reducing malondialdehyde levels, increasing acetylcholine levels, expression levels of α7 nicotinic acetylcholine receptor (α7nAChR), nuclear factor erythrocyte 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in the hippocampus. Above all, SAM has a potential neuroprotective effect on ameliorating cognitive impairment in brain aging, which is related to inhibition of oxidative stress and neuroinflammation, as well as α7nAChR signals. DATA AVAILABILITY: Data will be made available on request.
Asunto(s)
Disfunción Cognitiva , Fármacos Neuroprotectores , Ratas , Animales , Antioxidantes/farmacología , S-Adenosilmetionina/metabolismo , S-Adenosilmetionina/farmacología , S-Adenosilmetionina/uso terapéutico , Galactosa/efectos adversos , Galactosa/metabolismo , Enfermedades Neuroinflamatorias , Receptor Nicotínico de Acetilcolina alfa 7/metabolismo , Estrés Oxidativo , Disfunción Cognitiva/metabolismo , Encéfalo/metabolismo , Hipocampo/metabolismo , Fármacos Neuroprotectores/farmacologíaRESUMEN
The native T1 values of the myocardium provide valuable information for tissue characterization and assessment of cardiomyopathies. In this study, we proposed a novel hybrid MOLLI sequence for myocardial T1 mapping. Unlike the two groups of inversion-recovery sampling of the conventional MOLLI5(3 s)3 sequence, the hybrid MOLLI sequence consisted of an inversion-recovery block followed by a saturation-recovery block. Since the second block employed a saturation pulse to spoil the longitudinal magnetization, it did not require a waiting period as MOLLI5(3 s)3 did. As a result, the hybrid MOLLI required less acquisition time leading to a practical application for patients with breath-hold difficulties. Phantom and healthy subject experiments were performed to evaluate the proposed sequence against the MOLLI5(3 s)3 sequence. The phantom study showed that the heart-rate dependency of one variant of the hybrid MOLLI sequences, hbMOLLI4, was comparable to that of MOLLI5(3 s)3. In addition, both hbMOLLI4 and MOLLI53 derived T1 values under 2% variations with simulated heart rates from 50 to 90 beats-per-minute within the range of T1 values for myocardium and blood before contrast administration. Simulation results suggested slightly reduced T1 fitting precision in hbMOLLI4 compared with MOLLI5(3 s)3, but prominently better than saturation recovery. Bland-Altman analysis on accuracy assessment revealed that hbMOLLI4 partially reduced the T1 underestimation of MOLLI5(3 s)3. In the human study, The T1 values of both methods were consistent (hbMOLLI4 vs. MOLLI5(3 s)3, slope = 1.14, R2 > 0.97), with equal reproducibility. The results supported that hybrid MOLLI produced comparable T1 mapping results in terms of accuracy, reproducibility, and heart-rate dependency, at the expense of slightly reduced precision. We concluded that the hybrid MOLLI sequence presents a competitive alternative to the MOLLI5(3 s)3 sequence when a speedy acquisition is required.
Asunto(s)
Cardiomiopatías , Imagen por Resonancia Magnética , Humanos , Reproducibilidad de los Resultados , Imagen por Resonancia Magnética/métodos , Corazón/diagnóstico por imagen , Miocardio , Fantasmas de ImagenRESUMEN
The addition of immune checkpoint blockade (ICB) to cytotoxic chemotherapy has emerged as the first-line treatment for multiple cancers. Paradoxically, cytotoxic chemotherapy may limit the therapeutic potential of ICB by significantly impairing the largest immune organ, the gastrointestinal (GI) tract, and driving gut microbial dysbiosis. Here, an orally administered polymeric adsorbent containing a supramolecular motif (named SPORA-SN9) is reported, which can selectively remove chemotherapeutics from the GI tract, thereby preventing chemotherapy-induced GI mucositis and microbial dysbiosis and providing better chemoimmunotherapy synergy. By theoretical design and experimental screening of the molecular recognition motifs, SPORA-SN9 exhibits superior complexation capacity for doxorubicin and irinotecan and high selectivity over a range of commonly used combinational medications. In mouse models of chemotherapy-induced GI mucositis, SPORA-SN9 protects the integrity of the GI tissues and the homeostasis of the gut microbiota. Finally, the addition of SPORA-SN9 enhances the efficacy of chemoimmunotherapy in tumor-bearing mice. SPORA-SN9 offers a translational approach for supramolecular chemistry to modulate complex biosystems by selectively removing target substrates from the GI tract.
Asunto(s)
Antineoplásicos , Microbioma Gastrointestinal , Mucositis , Neoplasias , Ratones , Animales , Disbiosis/tratamiento farmacológico , Mucositis/inducido químicamente , Mucositis/tratamiento farmacológico , Mucositis/prevención & control , Neoplasias/tratamiento farmacológico , Antineoplásicos/uso terapéuticoRESUMEN
The combination of gene therapy and chemotherapy is emerging as a promising strategy for multidrug-resistant (MDR) cancer treatment. However, due to the significant differences in the physicochemical properties between macromolecular oligonucleotides and chemodrugs, the co-delivery of different drug combos makes for a great challenge. Moreover, the biosafety of the carriers and poor lysosomal escape of oligonucleotides are the main concerns for combination therapy. Herein, we developed a facile carrier-free strategy to co-deliver small interfering RNA (siRNA) and positive-charged chemodrugs (termed cationic amphiphilic chemodrugs, CACDs), in which CACDs interact with negative-charged anti P-glycoprotein siRNA (siPgp) without extra carriers and self-assemble into siPgp/CACDs nanoparticles (NPs[siPgp/CACDs]). Meanwhile, the CACDs also play an important role in the lysosomal escape of siRNA. Both molecular dynamics simulations and experimental characterization demonstrate that CACDs and siRNA can self-assemble into nanoparticles. Furthermore, red blood cell membrane (RBCm) was used to camouflage the NPs[siPgp/CACDs] to enhance their physiological stability and prolong the circulation time. Both in vitro and in vivo assessments reveal their excellent performance for drug-resistant cancer treatment. This strategy provides a safe and efficient pathway for gene and chemo combination therapy for MDR cancers.
Asunto(s)
Nanopartículas , Neoplasias , Humanos , ARN Interferente Pequeño , Membrana Eritrocítica , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Oligonucleótidos , Línea Celular TumoralRESUMEN
Liposomes and polymersomes, typical vesicular drug delivery systems (DDSs), have faced some limitations in cancer theranostics. Suprasomes, supramolecular vesicles assembled from amphiphiles linked by noncovalent interactions, show potential as new generation of vesicular DDSs. We construct suprasomes based on host-guest recognition, by which the desired functions can be integrated into carriers without tedious synthesis. Photothermally active host-guest complex is formed between a functional guest and pillar[5]arene, which further self-assembles into hollow suprasomes. A supramolecular nanomedicine is developed by encapsulating cisplatin in the suprasomes. The obtained cisplatin@Suprasomes achieve excellent anticancer efficacy and anti-metastasis combining chemotherapy and photothermal therapy, which ablate the tumors without relapse and metastasis. This work demonstrates the facile functionalization of suprasomes, holding promise as alternatives to liposomes and polymersomes.