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The practical application of Na-based solid-state electrolytes (SSEs) is limited by their low level of conduction. To evaluate the impact of tetrahedral anion groups on carrier migration, we designed a set of anti-perovskite SSEs theoretically based on the previously reported Na4OBr2, including Na4O(BH4)2, Na4O(BF4)2, and Na4O(AlH4)2. It is essential to note that the excessive radius of anionic groups inevitably leads to lattice distortion, resulting in asymmetric migration paths and a limited improvement in carrier migration rate. Na4O(AlH4)2 provides a clear example of where Na+ migrates in two distinct environments. In addition, due to different spatial charge distributions, the interaction strength between anionic groups and Na+ is different. Strong interactions can cause carriers to appear on a swing, leading to a decrease in conductivity. The low conductivity of Na4O(BF4)2 is a typical example. This study demonstrates that Na4O(BH4)2 exhibits remarkable mechanical and dynamic stability and shows ionic conductivity of 1.09 × 10-4 S cm-1, two orders of magnitude higher than that of Na4OBr2. This is attributed to the expansion of the carrier migration channels by the anion groups, the moderate interaction between carriers and anionic groups, and the "paddle-wheel" effect generated by the anion groups, indicating that the "paddle-wheel" effect is still effective in low-dimensional anti-perovskite structures, in which atoms are arranged asymmetrically.
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Pd/CeO2 catalysts show superior catalytic performance owing to their optimal cycling activity and stability. In this study, single-atom Pd and eight-atom Pd nanoparticle clusters were supported on the surface of CeO2(110) to investigate the effect of loaded-metal size on the catalytic performance of the Pd-CeO2 system for CO2 reduction. We investigated the CO2 reduction reaction (CRR) that produces C1 products (CO, HCOOH, CH3OH, and CH4) on Pd8/CeO2 and Pd/CeO2 by density functional theory. The structures, CO2 adsorption configurations, and CO2 reduction mechanisms of these two electrocatalysts were systematically studied. Subsequently, different reduction pathways on Pd8/CeO2 and Pd/CeO2 were investigated to identify the optimal reaction pathway for further assessment. The results showed that both of these catalysts are more selective towards the production of CH3OH than CH4. Moreover, compared to Pd/CeO2 and Pd4/CeO2 (from a previously reported study) the production of CH3OH via the CRR on Pd8/CeO2 exhibited the lowest limiting potential. These results demonstrate the superiority of Pd8/CeO2 as an electrocatalyst for the electrochemical reduction of CO2 to CH3OH.
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Mesoporous carriers have been widely used to deliver anticancer drugs due to their unique characteristics. In this work, mesoporous silica nanoparticles (MSN) and mesoporous carbon nanoparticles (MCN) with substantially similar and uniform particle size, specific surface area, and pore size were prepared to compare the photothermal effect, drug loading efficiencies (LE), and drug release properties. In order to improve the dispersion stability and biocompatibility of the carriers, MSN and MCN were grafted with PEG, respectively. The NIR-induced photothermal effect results indicated that MCN had a brilliant photothermal conversion efficiency due to its strong near-infrared absorption capacity, while MSN had no photothermal conversion capability. Moreover, LE of DOX in DOX/MCN-PEG reached 36.58%, higher than that in DOX/MSN-PEG, which was ascribed to non-covalent interaction of π-π stacking and electrostatic attraction. In addition, compared to DOX/MSN-PEG, DOX/MCN-PEG had a significantly increased release rate under NIR laser irradiation due to excellent photothermal conversion capability of MCN-PEG. Furthermore, cell viability assay and cellular uptake experiment results demonstrated that DOX/MCN-PEG showed a synergistic therapeutic effect in the combination of chemotherapy and phototherapy, with a combination index (CI) of 0.238.
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Antineoplásicos/administração & dosagem , Antineoplásicos/química , Carbono/química , Nanopartículas/química , Dióxido de Silício/química , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacocinética , Antineoplásicos/farmacocinética , Linhagem Celular , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Doxorrubicina/farmacocinética , Portadores de Fármacos , Composição de Medicamentos , Liberação Controlada de Fármacos , Excipientes , Hemólise/efeitos dos fármacos , Humanos , Tamanho da Partícula , Polietilenoglicóis , Porosidade , CoelhosRESUMO
In this research, a novel method was used to successfully stably coat Pluronic P123 on mesoporous silica nanoparticles (MSNs). Co-constructing a drug delivery system (DDS) with P123 and MSNs has not been previously reported. In this DDS, the coating of P123 was realized through a hydrophobic interaction with octadecyl chain-modified MSNs. The experiments found only Pluronic with an appropriate ratio of hydrophilic and lipophilic segments could keep the nanoassemblies stable. For comparison, nanoassemblies consisting of P123 and octadecyl chain-modified MSNs with or without a disulfide bond were prepared, which were denoted as PSMSNs and PMSNs, respectively. The disulfide bond was expected to endow the system with redox-responsiveness to enhance the therapeutic effect meanwhile decreasing the toxicity. A series of experiments including characterization of the nanoparticles, in vitro drug release, cell uptake and cellular drug release, in vitro cytotoxicity, cell migration and biodistribution of the nanoparticles were carried out. Compared with the PMSNs, PSMSNs displayed a redox-responsive drug release property not only in in vitro release text, but also on the cellular level. In addition, the cell migration experiments proved that the coating of P123 endowed the system with the ability of anti-metastasis. The accumulation of P123 in the tumor was enhanced after coating the MSNs by virtue of the 'EPR' effect of nanoparticles compared with the solution form.
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Materiais Revestidos Biocompatíveis/química , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas/química , Neoplasias/tratamento farmacológico , Poloxâmero/química , Dióxido de Silício/química , Adsorção , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Feminino , Humanos , Camundongos Endogâmicos BALB C , Nanopartículas/ultraestrutura , Nitrogênio/química , Oxirredução , Porosidade , Distribuição Tecidual/efeitos dos fármacos , Cicatrização/efeitos dos fármacosRESUMO
A structurally controllable fluorescence-labeled hollow mesoporous carbon (HMC) was simply prepared to improve the oral bioavailability of insoluble drugs and further trace their delivery process in vivo. The hollow structure was derived from an inverse replica process using mesoporous silica as a template and the fluorescent label was prepared by doping the carboxylated HMC with a confinement of Eu(3+)/Gd(3+)-EDTA. The physicochemical properties of the composites were systematically characterized by transmission electron microscopy, Fourier transform infrared spectroscopy and photoluminescence spectra tests prior to studying their effects on drug-release behavior and biodistribution. As a result, the thickness of the carrier's shell was adjusted from 70 nm to 130 nm and the maximum drug loading was up to 73.6%. The model drug carvedilol (CAR) showed sustained release behavior compared to CAR commercial capsules, and the dissolution rate slowed down as the shells got thicker. AUC0-48h and Tmax were enlarged 2.2 and 6.5 fold, respectively, which demonstrated that oral bioavailability was successfully improved. Bioimaging tests showed that the novel carbon vehicle had a long residence time in the gastrointestinal tract. In short, the newly designed HMC is a promising drug carrier for both oral bioavailability improvement and in vivo tracing.
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Carbono/química , Disponibilidade Biológica , Portadores de Fármacos , Ácido Edético , Európio , Gadolínio , Porosidade , Dióxido de Silício , Solubilidade , Distribuição TecidualRESUMO
OBJECTIVE: To explore the effect of the pore size of three-dimensionally ordered macroporous chitosan-silica (3D-CS) matrix on the solubility, drug release, and oral bioavailability of the loaded drug. METHODS: 3D-CS matrices with pore sizes of 180 nm, 470 nm, and 930 nm were prepared. Nimodipine (NMDP) was used as the drug model. The morphology, specific surface area, and chitosan mass ratio of the 3D-CS matrices were characterized before the effect of the pore size on drug crystallinity, solubility, release, and in vivo pharmacokinetics were investigated. RESULTS: With the pore size of 3D-CS matrix decreasing, the drug crystallinity decreased and the aqueous solubility increased. The drug release was synthetically controlled by the pore size and chitosan content of 3D-CS matrix in a pH 6.8 medium, while in a pH 1.2 medium the erosion of the 3D-CS matrix played an important role in the decreased drug release rate. The area under the curve of the drug-loaded 3D-CS matrices with pore sizes of 930 nm, 470 nm, and 180 nm was 7.46-fold, 5.85-fold, and 3.75-fold larger than that of raw NMDP respectively. CONCLUSION: Our findings suggest that the oral bioavailability decreased with a decrease in the pore size of the matrix.
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Quitosana/farmacocinética , Liberação Controlada de Fármacos/fisiologia , Nimodipina/farmacocinética , Dióxido de Silício/farmacocinética , Administração Oral , Animais , Disponibilidade Biológica , Quitosana/administração & dosagem , Quitosana/química , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Liberação Controlada de Fármacos/efeitos dos fármacos , Conformação Molecular , Nimodipina/administração & dosagem , Nimodipina/química , Porosidade , Ratos , Ratos Sprague-Dawley , Dióxido de Silício/administração & dosagem , Dióxido de Silício/químicaRESUMO
PURPOSE: A novel mesoporous carbon/lipid bilayer nanocomposite (MCLN) with a core-shell structure was synthesized and characterized as an oral drug delivery system for poorly water-soluble drugs. The objective of this study was to investigate the potential of MCLN-based formulation to modulate the in vitro release and in vivo absorption of a model drug, nimodipine (NIM). METHODS: NIM-loaded MCLN was prepared by a procedure involving a combination of thin-film hydration and lyophilization. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), specific surface area analysis, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were employed to characterize the NIM-loaded MCLN formulation. The effect of MCLN on cell viability was assessed using the MTT assay. In addition, the oral bioavailability of NIM-loaded MCLN in beagle dogs was compared with that of the immediate-release formulation, Nimotop®. RESULTS: Our results demonstrate that the NIM-loaded MCLN formulation exhibited a typical sustained release pattern. The NIM-loaded MCLN formulation achieved a greater degree of absorption and longer lasting plasma drug levels compared with the commercial formulation. The relative bioavailability of NIM for NIM-loaded MCLN was 214%. MCLN exhibited negligible toxicity. CONCLUSION: The data reported herein suggest that the MCLN matrix is a promising carrier for controlling the drug release rate and improving the oral absorption of poorly water-soluble drugs.
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Carbono/química , Portadores de Fármacos/síntese química , Bicamadas Lipídicas/química , Nanocompostos/química , Nimodipina/administração & dosagem , Água/química , Administração Oral , Disponibilidade Biológica , Células CACO-2 , Varredura Diferencial de Calorimetria , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Liofilização , Células HT29 , Humanos , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Modelos Biológicos , Nimodipina/química , Nimodipina/farmacocinética , Porosidade , Solubilidade , Propriedades de Superfície , Difração de Raios XRESUMO
Cyclodextrin (CD)-capped mesoporous silica nanoparticles (MSN) with pH-responsive properties were synthesized, but little research has been carried out to evaluate the impact of critical factors such as the stalk density and the type of CD on the pH-responsive release behavior. Here, the effect of different stalk densities on the pH-responsive release behavior was investigated. Either too low or too high density of the grafted p-anisidine stalk could result in poor cargo release, and the optimum stalk density for MSN was measured by thermal analysis, and found to be approximately 8.7 stalks nm(-2). To achieve effective release control, the CD capes, α-CD and ß-CD, were also investigated. Isothermal titration calorimetry (ITC) analysis was employed to determine the formation constants (Kf) of the two CD with p-anisidine at different pH values. The results obtained showed that the complex of ß-CD with p-anisidine had excellent pH-responsive behavior as it exhibited the largest changed formation constant (ΔKf) in different pH media. Furthermore, the pH-responsive mechanism between CD and p-anisidine molecules was investigated through ITC and a molecular modeling study. The release of antitumor drug DOX presents a significant prospect toward the development of pH-responsive nanoparticles as a drug delivery vehicle.
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Ciclodextrinas/química , Portadores de Fármacos/química , Nanopartículas/química , Dióxido de Silício/química , Concentração de Íons de Hidrogênio , Modelos MolecularesRESUMO
In the past decade, mesoporous silica nanoparticles (MSNs) with a large surface area and pore volume have attracted considerable attention for their application in drug delivery and biomedicine. In this review, we highlight the recent advances in silica-assisted drug delivery systems, including (1) MSN-based immediate/sustained drug delivery systems and (2) MSN-based controlled/targeted drug delivery systems. In addition, we summarize the biomedical applications of MSNs, including (1) MSN-based biotherapeutic agent delivery; (2) MSN-assisted bioimaging applications; and (3) MSNs as bioactive materials for tissue regeneration. FROM THE CLINICAL EDITOR: This comprehensive review presents recent advances in mesoporous silica nanoparticles assisted drug delivery systems, including both immediate and sustained delivery systems as well as controlled release and targeted drug delivery systems. In addition to achieving therapeutic agent delivery, imaging applications and potential use of silica NPs in tissue regeneration are also discussed.
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Sistemas de Liberação de Medicamentos , Nanopartículas/uso terapêutico , Dióxido de Silício/uso terapêutico , Materiais Biocompatíveis/química , Materiais Biocompatíveis/uso terapêutico , Humanos , Nanopartículas/química , Porosidade , Dióxido de Silício/químicaRESUMO
Phototherapy, such as photothermal therapy (PTT) and photodynamic therapy (PDT), has been considered an elegant solution to eradicate tumors due to its minimal invasiveness and low systemic toxicity. Nevertheless, it is still challenging for phototherapy to achieve ideal outcomes and clinical translation due to its inherent drawbacks. Owing to the unique biological functions, diverse gases have attracted growing attention in combining with phototherapy to achieve super-additive therapeutic effects. Specifically, gases such as nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S) have been proven to kill tumor cells by inducing mitochondrial damage in synergy with phototherapy. Additionally, several gases not only enhance the thermal damage in PTT and the reactive oxygen species (ROS) production in PDT but also improve the tumor accumulation of photoactive agents. The inflammatory responses triggered by hyperthermia in PTT are also suppressed by the combination of gases. Herein, we comprehensively review the latest studies on gas-synergized phototherapy for cancer therapy, including (1) synergistic mechanisms of combining gases with phototherapy; (2) design of nanoplatforms for gas-synergized phototherapy; (3) multimodal therapy based on gas-synergized phototherapy; (4) imaging-guided gas-synergized phototherapy. Finally, the current challenges and future opportunities of gas-synergized phototherapy for tumor treatment are discussed. STATEMENT OF SIGNIFICANCE: 1. The novelty and significance of the work with respect to the existing literature. (1) Strategies to design nanoplatforms for gas-synergized anti-tumor phototherapy have been summarized for the first time. Meanwhile, the integration of various imaging technologies and therapy modalities which endow these nanoplatforms with advanced theranostic capabilities has been summarized. (2) The mechanisms by which gases synergize with phototherapy to eradicate tumors are innovatively and comprehensively summarized. 2. The scientific impact and interest. This review elaborates current trends in gas-synergized anti-tumor phototherapy, with special emphases on synergistic anti-tumor mechanisms and rational design of therapeutic nanoplatforms to achieve this synergistic therapy. It aims to provide valuable guidance for researchers in this field.
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Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Medicina de Precisão , Fototerapia/métodos , Gases/uso terapêutico , Neoplasias/patologia , Terapia Combinada , Nanopartículas/uso terapêutico , Linhagem Celular TumoralRESUMO
[This corrects the article DOI: 10.1016/j.apsb.2022.04.018.].
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Reactive oxygen species (ROS) generated from photosensitizers exhibit great potential for repolarizing immunosuppressive tumor-associated macrophages (TAMs) toward the anti-tumor M1 phenotype, representing a promising cancer immunotherapy strategy. Nevertheless, their effectiveness in eliminating solid tumors is generally limited by the instability and inadequate TAMs-specific targeting of photosensitizers. Here, a novel core-shell integrated nano platform is proposed to achieve a coordinated strategy of repolarizing TAMs for potentiating cancer immunotherapy. Colloidal mesoporous silica nanoparticles (CMSN) are fabricated to encapsulate photosensitizer-Indocyanine Green (ICG) to improve their stability. Then ginseng-derived exosome (GsE) was coated on the surface of ICG/CMSN for targeting TAMs, as well as repolarizing TAMs concurrently, named ICG/CMSN@GsE. As expected, with the synergism of ICG and GsE, ICG/CMSN@GsE exhibited better stability, mild generation of ROS, favorable specificity toward M2-like macrophages, enhancing drug retention in tumors and superior TAMs repolarization potency, then exerted a potent antitumor effect. In vivo, experiment results also confirm the synergistic suppression of tumor growth accompanied by the increased presence of anti-tumor M1-like macrophages and maximal tumor damage. Taken together, by integrating the superiorities of TAMs targeting specificity and synergistic TAMs repolarization effect into a single nanoplatform, ICG/CMSN@GsE can readily serve as a safe and high-performance nanoplatform for enhanced cancer immunotherapy.
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Mucosal immunization is a powerful weapon against viral infection. In this paper, large pore mesoporous silica nanoparticles (LMSN) with different particle sizes were synthesized for loading influenza split vaccine (SV) to explore the effect of nanoparticle sizes on mucosal immunization and adjuvant efficacy. Interestingly, it was found that among the three particle sizes of nanoparticles, only LMSN-M with around 250â¯nm could significantly enhance the mucosal immune effect of SV, possessing adjuvant effect. The results indicated that particle size affected the adjuvant effect of LMSN. There was no apparent difference in vaccine loading capacity of LMSN with different particle sizes, but the release of SV depended on the pore length of LMSN. The adjuvant effect of LMSN-M was attributed to its higher cellular uptake performance, intestine absorption and transport efficiency, and the ability to stimulate the maturation of dendritic cells. Simultaneously, compared with LMSN-S and LMSN-L, the more retention of LMSN-M in mesenteric lymph nodes increased the chance of interaction between vaccine and immune system, resulting in the enhanced immunity. This is the first time to study the impact of particle size of LMSN adjuvant on improving mucosal immunity of oral influenza vaccine, and the present work provides a scientific reference for adjuvant design of oral vaccine.
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Vacinas contra Influenza , Nanopartículas , Tamanho da Partícula , Dióxido de Silício , Dióxido de Silício/química , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/química , Vacinas contra Influenza/administração & dosagem , Nanopartículas/química , Animais , Administração Oral , Porosidade , Camundongos , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/administração & dosagem , Camundongos Endogâmicos BALB C , Feminino , Imunidade nas Mucosas/efeitos dos fármacos , Propriedades de SuperfícieRESUMO
Combination therapies have attracted significant attention because they address the limitations of monotherapy while improving overall efficacy. In this study, we designed a novel nanoplatform, named GOx@Fe-DMSN@PDA (GFDP), by integrating Fe2+ into dendritic mesoporous silica nanoparticles (DMSN) and selecting glucose oxidase (GOx) as the model drug loaded into the DMSN pores. Additionally, we coated the surface of the DMSN with polydopamine (PDA) to confer pH/near infrared (NIR) light-responsive controlled-release behavior and photothermal therapy (PTT). The introduction of Fe2+ into the DMSN framework greatly improved biodegradability and enhanced the peroxidase (POD)-like activity of GFDP. In addition, GOx could consume glucose and generate hydrogen peroxide (H2O2) within tumor cells to facilitate starvation therapy and enhance cascade catalysis. The PDA coating provided the DMSN with an intelligent response release ability, promoting efficient photothermal conversion and achieving the PTT effect. Cellular tests showed that under NIR light irradiation, GFDP exhibited a synergistic effect of PTT-enhanced starvation therapy and cascade catalysis, with a half-maximal inhibitory concentration (IC50) of 2.89 µg/mL, which was significantly lower than that of GFDP without NIR light irradiation (18.29 µg/mL). The in vivo anti-tumor effect indicated that GFDP could effectively accumulate at the tumor site for thermal imaging and showed remarkable synergistic therapeutic effects. In summary, GFDP is a promising nanoplatform for multi-modal combination therapy that integrates starvation therapy, PTT, and cascade catalysis.
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Photodynamic therapy (PDT) is limited in tumor therapy due to the mature antioxidant barrier of tumor microenvironment (TME) and phototoxicity/easy-degradation characteristics of photosensitizers. Therefore, we prepared Cu2+-doped hollow carbon nanoparticles (CHC) to protect the loaded photosensitizers and sensitize TME by glutathione-depletion and peroxidase (POD)-like activity for enhanced PDT. CHC significantly increased the maximum speed of POD-like reaction (Vm) of 8.4 times. By coating with hyaluronic acid (HA), the active sites on CHC were temporarily masked with low catalytic property, and restored in response to the overexpressed hyaluronidase in TME. Meanwhile, due to the excellent photothermal conversion efficiency (32.5 %) and hollow structure of CHC, the loaded photosensitizers were well protected from sunlight activation-induced unwanted phototoxicity and rapid degradation under the near-infrared light irradiation. In-vivo anti-tumor experiments demonstrated that the combination of photothermal-photodynamic effect achieved the best anti-tumor effect (tumor inhibition rate at 87.8 %) compared with any monotherapy. In addition, the combination of photothermal and photodynamic effect could efficiently suppress the cell migration, manifesting the reduced number of lung metastasized nodules by 74 %. This work provides an integrated platform for photosensitizers protection and TME sensitization for enhanced PDT.
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Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/química , Carbono/farmacologia , Microambiente Tumoral , Neoplasias/tratamento farmacológico , Catálise , Linhagem Celular Tumoral , Nanopartículas/química , Peróxido de HidrogênioRESUMO
Limited drug loading and incomplete drug release are two major obstacles that traditional polymeric microneedles (MNs) have to overcome. For smart controlled-release MNs, since drug release duration is uncertain, a clear indication of the finish of drug release is also important for patient guidance on the timing of the next dose. In this study, MN with a triple structure of a glucose-responsive shell, loaded insulin powders and a colored propelling inner core (inspired by the mechanism of osmotic pump) was innovatively constructed. The MN patch could release insulin according to blood glucose levels (BGLs) and had excellent drug loading, more complete drug release, and good drug stability, which significantly prolonged the normoglycemic time. An approximately 0.3 cm2 patch has a hypoglycemic effect on diabetic mice for up to 24 h. Moreover, the fading of the inner core could indicate the release process of the loaded drug and can help to facilitate uninterrupted closed loop therapy for patients. The designed triple MN structure is also suitable, and can be used in the design of other smart MN drug delivery systems to further improve their drug loading capacity and simultaneously achieve more complete, smart controlled and visualized drug release.
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Diabetes Mellitus Experimental , Humanos , Camundongos , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Agulhas , Sistemas de Liberação de Medicamentos , Insulina , Glucose , Administração CutâneaRESUMO
Junctional adhesion molecule 3 (JAM3) can be used as a prognostic marker in multiple cancer types. However, the potential prognostic role of JAM3 in gastric cancer (GC) remains unclear. The purpose of this research was to gauge JAM3 expression and methylation as potential biomarkers for GC patient survival. Through bioinformatics research, we analyzed JAM3 expression, methylation, prognosis, and immune cell infiltrations. JAM3 methylation acts as a negative regulator of JAM3, leading to reduced expression of JAM3 in GC tissues relative to normal tissues. Patients with GC who expressed little JAM3 have a better chance of living a long time free of the disease, according to the Cancer Genome Atlas (TCGA) database. Through univariate and multivariate Cox regression analysis, inadequate JAM3 expression was labeled as an isolated indicator for overall survival (OS). The GSE84437 dataset was also used to confirm JAM3 prognostic role in GC, with consistent findings. A meta-analysis also found that low levels of JAM3 expression were significantly associated with longer OS. Finally, there was a strong correlation between JAM3 expression and a subset of immune cells. According to the TCGA database, low JAM3 expression could predict favorable OS and progression-free-survival (PFS) in GC patients (P < .05). The univariate and multivariate Cox regression demonstrated that low JAM3 expression was independent biomarker for OS (P < .05). Moreover, GSE84437 dataset was utilized to verify the prognostic role of JAM3 in GC, and the similar results were reached (P < .05). A meta-analysis revealed that low JAM3 expression was closely relevant to better OS. Finally, JAM3 expression exhibited a close correlation with some immune cells (P < .05). JAM3 might be a viable predictive biomarker and likely plays a crucial part in immune cell infiltration in individuals with GC.
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Neoplasias Gástricas , Humanos , Biologia Computacional , Bases de Dados Factuais , Análise Multivariada , Estudos Observacionais como Assunto , Prognóstico , Neoplasias Gástricas/genéticaRESUMO
Glycolysis plays a vital role in the development and progression of tumors. Inhibiting glycolysis via smart and safe methods serves as a promising target for cancer therapy. Here, an oral "sugar-coated bullet" aiming at intervening Warburg effect is designed by coating colloidal mesoporous silica nanoparticles (CMS) encapsulating glycolysis inhibitor shikonin (SHK) with dextran, namely DCMS/SHK. The solubility and drug-loading capacity of SHK were enhanced by the special structure of CMS. Besides, the tempting bullets possess the spatial-to-point cascade targeting ability in delivering SHK from the colonic lumen to colon cancer cells and finally to PKM2. After DCMS/SHK reaches the colon, the dextran is hydrolyzed by dextranase especially existing in the colon site to glucose and the carriers become glucose-coated nanoparticles. The glucose-cloak nanoparticles would be largely endocytosed by tumor cells and complete the efficient delivery of SHK. The encapsulated SHK can prevent the glycolysis of cancer cells and thus inhibit tumor growth effectively. This work presents an ingenious cascade colon-targeting strategy to treat colon cancer by destroying cell energy metabolism.
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Neoplasias do Colo , Nanopartículas , Humanos , Açúcares , Dextranos , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Glucose , Neoplasias do Colo/tratamento farmacológico , Linhagem Celular TumoralRESUMO
The over-expressed GSH in tumor microenvironment significantly weakens the lethal reactive oxygen species (ROS) generated by photodynamic therapy (PDT) and catalysis of nanoenzyme. Hence, it is necessary to excavate a versatile and effective vehicle with oxidative stress-enhancement and GSH-depletion capacity to break the redox homeostasis in tumor microenvironment. GO has been reported to possess GSH-depletion and peroxidase (POD)-like capacity. Based on this, PEGylated mesoporous carbon (MC-PEG) was prepared as ICG vehicle to compare with PEGylated graphene oxide (GO-PEG). Excitingly, MC-PEG was found to exhibit three times higher oxidative capacity by POD-like process than GO-PEG, and owned more effective and continuous GSH-depletion capacity to further amplify the oxidative stress. Meanwhile, MC-PEG exhibited better protective effect on the loaded ICG against unwanted light excitation than GO-PEG. Together with the higher photothermal conversion effect, under the NIR light irradiation, MC-PEG could markedly improve the temperature of tumor cells and produce more hydroxyl radical, continuously consume GSH and provide more better protection for ICG compared with GO-PEG, thus further boosting the combination of photothermal and photodynamic effects. The anti-tumor experiment in cell and in-vivo level both validated that ICG/MC-PEG showed better synergistic effect with lower IC50 value and higher tumor suppression rate than ICG/GO-PEG.
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Fotoquimioterapia , Fototerapia , Carbono , Corantes , Polietilenoglicóis , Linhagem Celular TumoralRESUMO
Wound healing is a crucial process that restores the integrity and function of the skin and other tissues after injury. However, external factors, such as infection and inflammation, can impair wound healing and cause severe tissue damage. Therefore, developing new drugs or methods to promote wound healing is of great significance. Photothermal therapy (PTT) is a promising technique that uses photothermal agents (PTAs) to convert near-infrared radiation into heat, which can eliminate bacteria and stimulate tissue regeneration. PTT has the advantages of high efficiency, controllability, and low drug resistance. Hence, nanomaterial-based PTT and its related strategies have been widely explored for wound healing applications. However, a comprehensive review of PTT-related strategies for wound healing is still lacking. In this review, we introduce the physiological mechanisms and influencing factors of wound healing, and summarize the types of PTAs commonly used for wound healing. Then, we discuss the strategies for designing nanocomposites for multimodal combination treatment of wounds. Moreover, we review methods to improve the therapeutic efficacy of PTT for wound healing, such as selecting the appropriate wound dressing form, controlling drug release, and changing the infrared irradiation window. Finally, we address the challenges of PTT in wound healing and suggest future directions.