RESUMO
Osteosarcoma, a malignant bone tumor often characterized by high hedgehog signaling activity, residual tumor cells, and substantial bone defects, poses significant challenges to both treatment response and postsurgical recovery. Here, we developed a nanocomposite hydrogel for the sustained co-delivery of bioactive magnesium ions, anti-PD-L1 antibody (αPD-L1), and hedgehog pathway antagonist vismodegib, to eradicate residual tumor cells while promoting bone regeneration post-surgery. In a mouse model of tibia osteosarcoma, this hydrogel-mediated combination therapy led to remarkable tumor growth inhibition and hence increased animal survival by enhancing the activity of tumor-suppressed CD8+ T cells. Meanwhile, the implanted hydrogel improved the microenvironment of osteogenesis through long-term sustained release of Mg2+, facilitating bone defect repair by upregulating the expression of osteogenic genes. After 21 days, the expression levels of ALP, COL1, RUNX2, and BGLAP in the Vis-αPD-L1-Gel group were approximately 4.1, 5.1, 5.5, and 3.4 times higher than those of the control, respectively. We believe that this hydrogel-based combination therapy offers a potentially valuable strategy for treating osteosarcoma and addressing the tumor-related complex bone diseases.
Assuntos
Neoplasias Ósseas , Hidrogéis , Imunoterapia , Nanocompostos , Osteossarcoma , Osteossarcoma/patologia , Osteossarcoma/tratamento farmacológico , Osteossarcoma/terapia , Animais , Hidrogéis/química , Nanocompostos/química , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Neoplasias Ósseas/terapia , Camundongos , Imunoterapia/métodos , Linhagem Celular Tumoral , Regeneração Óssea/efeitos dos fármacos , Humanos , Osteogênese/efeitos dos fármacos , Antígeno B7-H1/metabolismo , Camundongos Endogâmicos BALB C , Magnésio/químicaRESUMO
Chemodynamic therapy (CDT) and photothermal therapy (PTT) have both demonstrated considerable efficacy in the tumor treatment individually, owing to their non-invasive nature and excellent selectivity. However, due to the propensity of tumors for metastasis and recurrence, a singular therapeutic approach falls short of achieving optimal treatment outcomes. Polydopamine (PDA) has excellent photothermal conversion ability and polyoxometalates (POMs) possess diverse enzymatic activities. Here, we synthesized PDA@POM nanospheres comprising polydopamine-coated Tungsten-based polyoxometalate (W-POM). These nanospheres leverage dual enzymatic activities that synergistically enhance both chemodynamic and photothermal therapies for tumor treatment. The PDA-mediated PTT effect enables precise tumor cell destruction, while the W-POM nanozymes catalyzes the generation of highly toxic reactive oxygen species (ROS) from hydrogen peroxide within tumor cells through a Fenton-like reaction, which mitigates tumor hypoxia and induces tumor cell death. This synergistic photothermal catalytic therapy shows enhanced efficacy in tumor suppression, providing a promising new approach for tumor treatment.
Assuntos
Antineoplásicos , Indóis , Nanocompostos , Polímeros , Indóis/química , Indóis/farmacologia , Nanocompostos/química , Polímeros/química , Polímeros/farmacologia , Animais , Humanos , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/química , Espécies Reativas de Oxigênio/metabolismo , Terapia Fototérmica , Sobrevivência Celular/efeitos dos fármacos , Fototerapia , Ensaios de Seleção de Medicamentos Antitumorais , Compostos de Tungstênio/química , Compostos de Tungstênio/farmacologia , Linhagem Celular Tumoral , Tamanho da Partícula , Propriedades de Superfície , Proliferação de Células/efeitos dos fármacos , Polieletrólitos , ÂnionsRESUMO
It is still a challenge to develop hierarchically nanostructured catalysts with simple approaches to enhance the low-temperature catalytic activity. Herein, a set of mesoporous Co-Cu binary metal oxides with different morphologies were successfully prepared via a facile ammonium bicarbonate precipitation method without any templates or surfactants, which were further applied for catalytic removal of carcinogenic toluene. Among the catalysts with different ratios, the CoCu0.2 composite oxide presented the best performance, where the temperature required for 90% conversion of toluene was only 237°C at the high weight hour space velocity (WHSV) of 240,000 mL/(gcat·hr). Meanwhile, compared to the related Co-Cu composite oxides prepared by using different precipitants (NaOH and H2C2O4), the NH4HCO3-derived CoCu0.2 sample exhibited better catalytic efficiency in toluene oxidation, while the T90 were 22 and 28°C lower than those samples prepared by NaOH and H2C2O4 routes, respectively. Based on various characterizations, it could be deduced that the excellent performance was related to the small crystal size (6.7 nm), large specific surface area (77.0 m2/g), hollow hierarchical nanostructure with abundant high valence Co ions and adsorbed oxygen species. In situ DRIFTS further revealed that the possible reaction pathway for the toluene oxidation over CoCu0.2 catalyst followed the route of absorbed toluene â benzyl alcohol â benzaldehyde â benzoic acid â carbonate â CO2 and H2O. In addition, CoCu0.2 sample could keep stable with long-time operation and occur little inactivation under humid condition (5 vol.% water), which revealed that the NH4HCO3-derived CoCu0.2 nanocatalyst possessed great potential in industrial applications for VOCs abatement.
Assuntos
Cobre , Nanocompostos , Catálise , Nanocompostos/química , Cobre/química , Compostos Orgânicos Voláteis/química , Cobalto/química , Porosidade , Poluentes Atmosféricos/química , Tolueno/química , TemperaturaRESUMO
Selective and sensitive sarcosine detection is crucial due to its recent endorsement as a prostate cancer (PCa) biomarker in clinical diagnosis. The reduced graphene oxide-cobalt nickel tungsten boron oxides (CoNiWBO/rGO) nanocomposite is developed as a non-enzymatic electrochemical sensor for sarcosine detection in PCa patients' serum. CoNiWBO/rGO is synthesized by the chemical reduction method via a one-pot reduction method followed by calcination at 500 °C under a nitrogen environment for 2 h and characterized by UV-Vis, XRD, TGA, and SEM. CoNiWBO/rGO is then deposited on a glassy carbon electrode, and sarcosine sensing parameters are optimized, including concentration and pH. This non-enzymatic sensor is employed to directly determine sarcosine in serum samples. Differential pulse voltammetry (DPV) and linear sweep voltammetry (LSV) are employed to monitor the electrochemical behavior where sarcosine binding leads to oxidation. Chronoamperometric studies show the stability of the developed sensor. The results demonstrate a wide linear range from 0.1 to 50 µM and low limits of detection, i.e., 0.04 µM and 0.07 µM using DPV and LSV respectivel. Moreover, the calculated recovery of sarcosine in human serum of prostate cancer patients is 78-96%. The developed electrochemical sensor for sarcosine detection can have potential applications in clinical diagnosis.
Assuntos
Técnicas Eletroquímicas , Grafite , Nanocompostos , Níquel , Neoplasias da Próstata , Sarcosina , Humanos , Sarcosina/sangue , Masculino , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Nanocompostos/química , Grafite/química , Técnicas Eletroquímicas/métodos , Níquel/sangue , Níquel/química , Tungstênio/química , Cobalto/sangue , Óxidos/química , Biomarcadores Tumorais/sangue , Limite de Detecção , EletrodosRESUMO
This work aimed to fabricate a Cloisite 30B-incorporated carboxymethyl cellulose graft copolymer of acrylic acid and itaconic acid hydrogel (Hyd) via a free radical polymerization method for controlled release of Sunitinib malate anticancer drug. The synthesized samples were characterized by FTIR, XRD, TEM, and SEM-dot mapping analyses. The encapsulation efficiency of Hyd and Hyd/Cloisite 30B (6 wt%) was 81 and 93%, respectively, showing the effectiveness of Cloisite 30B in drug loading. An in vitro drug release study showed that drug release from all samples in a buffer solution with pH 7.4 was higher than in a buffer solution with pH 5.5. During 240 min, the cumulative drug release from Hyd/Cloisite 30B (94.97% at pH 7.4) is lower than Hyd (53.71% at pH 7.4). Also, drug-loaded Hyd/Cloisite 30B (6 wt%) demonstrated better antibacterial activity towards S. Aureus bacteria and E. Coli. High anticancer activity of Hyd/Cloisite 30B against MCF-7 human breast cancer cells was shown by the MTT assay, with a MCF-7 cell viability of 23.82 ± 1.23% after 72-hour incubation. Our results suggest that Hyd/Cloisite 30B could be used as a pH-controlled carrier to deliver anticancer Sunitinib malate.
Assuntos
Carboximetilcelulose Sódica , Portadores de Fármacos , Hidrogéis , Indóis , Nanocompostos , Pirróis , Succinatos , Sunitinibe , Sunitinibe/química , Sunitinibe/farmacologia , Humanos , Concentração de Íons de Hidrogênio , Succinatos/química , Succinatos/farmacologia , Carboximetilcelulose Sódica/química , Hidrogéis/química , Indóis/química , Indóis/farmacologia , Nanocompostos/química , Pirróis/química , Pirróis/farmacologia , Portadores de Fármacos/química , Células MCF-7 , Antineoplásicos/farmacologia , Antineoplásicos/química , Resinas Acrílicas/química , Administração Oral , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/administração & dosagem , Liberação Controlada de Fármacos , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacosRESUMO
Early diagnosis and treatment of gastric cancer (GC) play a vital role in improving efficacy, reducing mortality and prolonging patients' lives. Given the importance of early detection of gastric cancer, an electrochemical biosensor was developed for the ultrasensitive detection of miR-19b-3p by integrating MoS2-based nanozymes, hybridization chain reaction (HCR) with enzyme catalyzed reaction. The as-prepared MoS2-based nanocomposites were used as substrate materials to construct nanoprobes, which can simultaneously load probe DNA and HCR initiator for signal amplification. Moreover, the MoS2-based nanocomposites are also employed as nanozymes to amplify electrochemical response. The presence of miR-19b-3p induced the assembly of MoS2-based nanoprobes on the electrode surface, which can activate in-situ HCR reaction to load a large number of horseradish peroxidase (HRP) for signal amplification. Coupling with the co-catalytic ability of HRP and MoS2-based nanozymes, the designed electrochemical biosensor can detect as low as 0.7 aM miR-19b-3p. More importantly, this biosensor can efficiently analyze miR-19b-3p in clinical samples from healthy people and gastric cancer patients due to its excellent sensitivity and selectivity, suggesting that this biosensor has a potential application in early diagnosis of disease.
Assuntos
Técnicas Biossensoriais , Dissulfetos , Técnicas Eletroquímicas , Peroxidase do Rábano Silvestre , MicroRNAs , Molibdênio , Neoplasias Gástricas , Neoplasias Gástricas/diagnóstico , Humanos , MicroRNAs/genética , Molibdênio/química , Técnicas Eletroquímicas/métodos , Peroxidase do Rábano Silvestre/química , Peroxidase do Rábano Silvestre/metabolismo , Técnicas Biossensoriais/métodos , Dissulfetos/química , Hibridização de Ácido Nucleico , Nanocompostos/química , Limite de DetecçãoRESUMO
OBJECTIVE: To study the optical properties of nanocomposites as well as antibacterial activity. METHODS: The experimental study was conducted at the University of Babylon, College of Science and College of Education for Pure Sciences, Babylon, Iraq, from September 2021 to February 2022. Impregnation of transparent matrix polyvinyl alcohol and polyvinyl pyrrolidone nanocomposites was done by silver oxide and niobium oxide nanoparticles. The nanostructures were created using different ratios of polymer matrix, silver oxide nanoparticles and niobium oxide nanoparticles. The optical features of these nanocomposites were examined, whereby the latter type of properties was tested within the wavelength range of 220-820nm. The determination of the anti-microbial activity was done by disc diffusion method. The anti-bacterial activity involved gram-positive and gram-negative organisms. Different bacteria were cultured with Muller-Hinton medium. RESULTS: Absorbance, absorption coefficients and optical conductivity of the nanocomposites increased with the increase in nanocomposite concentrations. The energy gap for silver oxide and niobium oxide nanoparticles decreased when the concentrations of the nanoparticles increased. CONCLUSIONS: Promising outcomes may be achieved for the nanocomposites in anti-bacterial applications as the inhibition zones increased along with increased ratio of silver oxide and niobium oxide nanoparticles.
Assuntos
Antibacterianos , Nanocompostos , Nióbio , Óxidos , Álcool de Polivinil , Povidona , Compostos de Prata , Nanocompostos/química , Álcool de Polivinil/química , Álcool de Polivinil/farmacologia , Antibacterianos/farmacologia , Nióbio/farmacologia , Nióbio/química , Óxidos/farmacologia , Óxidos/química , Povidona/farmacologia , Povidona/química , Compostos de Prata/farmacologia , Compostos de Prata/química , Testes de Sensibilidade MicrobianaRESUMO
This research used a magnetic AlFu nano-metal-organic framework as an adsorbent for the first time. This approach extracts and preconcentrates eight pesticides from various distillates through a two-step process: magnetic dispersive micro solid phase extraction and dispersive liquid-liquid microextraction. Initially, the nanocomposite is dispersed into a sample solution containing the pesticides and Na2SO4. The target pesticides are then adsorbed onto the nanocomposite, which is subsequently isolated from the aqueous phase using an external magnetic field. Acetonitrile is used to elute the adsorbed analytes pesticides from the nanocomposite surface. The resulting acetonitrile extract, containing the concentrated pesticides, is then mixed with a tiny amount of another solvent and injected into a NaCl solution. Centrifugation allows the organic phase, enriched with the pesticides, to settle down. An aliquot of this organic layer is then analyzed using a gas chromatography-flame ionization detector. Optimization of the procedure led to favorable performance, including good extraction recovery of the pesticides (68-98 %), significant enrichment (enrichment factors of 340-489), a wide range of detectable concentrations (2.90-1400 µg L-1), and low detection (0.15-0.88 µg L-1) and quantification limits. (0.49-2.90 µg L-1).
Assuntos
Limite de Detecção , Microextração em Fase Líquida , Estruturas Metalorgânicas , Nanocompostos , Praguicidas , Nanocompostos/química , Praguicidas/isolamento & purificação , Praguicidas/análise , Praguicidas/química , Microextração em Fase Líquida/métodos , Estruturas Metalorgânicas/química , Adsorção , Cromatografia Gasosa/métodos , Microextração em Fase Sólida/métodos , Acetonitrilas/química , Extração em Fase Sólida/métodosRESUMO
In this study, an eco-friendly and novel hydrogel based on a crosslinked polyvinyl alcohol (PVA), iota carrageenan (IC) and polyvinylpyrrolidone (PVP) scaffold, containing a large amount (10-50â¯wt%) of nanoscale palm fronds (NPF) as additives, for water purification was demonstrated. A life cycle assessment (LCA) findings on NPF as biomass waste incorporated into PVA_PVP_IC polymer matrix was presented, and the results highlight the necessity of focused actions to reduce environmental impact and support the palm waste utilization in a sustainable manner. The multicomponent nanocomposite hydrogels were examined as adsorbents in a system work in batches for methylene blue (MB) and paracetamol (PCT) removal. The results show that, the presence of NPF, which dispersed in the hydrogel PVA_PVP_IC scaffolds containing both covalent and non-covalent cross-linking bonds, greatly enhanced the MB and PCT adsorption efficiency. A response surface methodology (RSM) model was used to find the best operating parameters of contaminant adsorption, including time, adsorbent dose, and starting concentration of pollutants. By using this statistical model, it was found that the optimal conditions for the adsorption reaction to achieve the complete removal of MB are 66.7â¯h adsorption time duration, 98.5â¯mgâ¯L-1 starting concentration, and an adsorbent dose of 5.9â¯mg, while for the complete removal of PCT, it is 57.6â¯h adsorption time duration, 80â¯mgâ¯L-1 starting concentration, and an adsorbent dose of 6â¯mg. The reusability of the nanocomposite hydrogels were tested for 5 cycles, all showed high adsorption capacity, indicating the potential for practical application of this nanocomposite hydrogel system. This study indicates that the prepared nanocomposite hydrogel raises the standard used for treatment of wastewater and also gives a solution to protect the environment and mitigate global warming.
Assuntos
Acetaminofen , Hidrogéis , Azul de Metileno , Nanocompostos , Álcool de Polivinil , Poluentes Químicos da Água , Purificação da Água , Azul de Metileno/química , Adsorção , Álcool de Polivinil/química , Poluentes Químicos da Água/química , Nanocompostos/química , Acetaminofen/química , Purificação da Água/métodos , Hidrogéis/química , Povidona/química , Carragenina/químicaRESUMO
An electrochemical biosensor was created to identify the liver cancer marker alpha-fetoprotein (AFP) by employing nanocomposite materials. A combination of reduced graphene oxide (rGO) and molybdenum disulfide (MoS2) was selected as the substrate material for the sensor to prepare the PtNPs/MoS2@rGO electrochemical immunosensor. Among them, rGO has strong conductivity and MoS2 provides a large surface area for the anchoring of PtNPs for better attachment to the hybridized nanomaterials. Meanwhile, PtNPs exhibit consistent biocompatibility and excellent electrocatalytic activity. PtNPs also attach to hybrid nanomaterials and bind the antibody via the Pt-S bond, thereby furnishing the antibody with multiple binding sites for enhanced antibody adhesion. The immunosensor achieved ultra-sensitive AFP detection by exploiting the specific antigen-antibody binding. The structure and morphology of the PtNPs/MoS2@rGO composites were investigated by transmission electron microscopy (TEM), energy dispersive X-ray (EDS) spectroscopy, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy, and the sensor was electrochemically characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Under optimized conditions, using differential pulse voltammetry the biosensor detected AFP in serum within a linear range of 1 ~ 105 pg/mL, with a correlation coefficient (r2) of 0.9989, and a detection limit of 0.12 pg/mL (S/N = 3). The method offers a new approach for the ultrasensitive detection of serum AFP and is extremely selective, accurate, and precise with a relative standard deviation (RSD) of less than 6%. It has been successfully applied to the analysis of real human blood samples.
Assuntos
Técnicas Biossensoriais , Dissulfetos , Técnicas Eletroquímicas , Grafite , Limite de Detecção , Nanopartículas Metálicas , Molibdênio , Platina , alfa-Fetoproteínas , Humanos , alfa-Fetoproteínas/análise , alfa-Fetoproteínas/imunologia , Molibdênio/química , Grafite/química , Platina/química , Técnicas Eletroquímicas/métodos , Dissulfetos/química , Técnicas Biossensoriais/métodos , Imunoensaio/métodos , Nanopartículas Metálicas/química , Anticorpos Imobilizados/imunologia , Anticorpos Imobilizados/química , Nanocompostos/químicaRESUMO
BACKGROUND: The world society is still suffering greatly from waterborne infections, with developing countries bearing most of the morbidity and death burden, especially concerning young children. Moreover, microbial resistance is one of the most prevalent global problems that extends the need for self-medication and the healing period, or it may be linked to treatment failure that results in further hospitalization, higher healthcare expenses, and higher mortality rates. Thus, innovative synthesis of new antimicrobial materials is required to preserve the environment and enhance human health. RESULTS: The present study highlighted a simple and cost-effective approach to biosynthesize a chitosan/graphene oxide/zinc oxide nanocomposite (CS/GO/ZnO) alone and immobilized in a macroporous cryogel as a new antimicrobial agent. Bacillus subtilis ATCC 6633 was used as a safe and efficient bio-nano-factory during biosynthesis. The formation of CS/GO/ZnO was confirmed and characterized using different analyses including ultraviolet-visible spectroscopy (UV-Vis), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), selective area diffraction pattern (SADP), Zeta analyses, scanning electron microscope (SEM) and transmission electron microscopy (TEM). GO combined with ZnO NPs successfully and displayed an adsorption peak at 358 nm. The XRD results showed the crystalline composition of the loaded ZnO NPs on GO sheets. FTIR spectrum confirmed the presence of proteins during the synthesis which act as stabilizing and capping agents. The nanocomposite has a high negative surface charge (-32.8 ± 5.7 mV) which increases its stability. SEM and TEM showing the size of biosynthesized ZnO-NPs was in the range of 40-50 nm. The CS/GO/ZnO alone or immobilized in cryogel revealed good antimicrobial activities against B. cereus ATCC 14,579, Escherichia coli ATCC 25,922, and Candida albicans ATCC 10,231 in a dose-dependent manner. The CS/GO/ZnO cryogel revealed higher antimicrobial activity than GO/ZnO nanocomposite and standard antibiotics (amoxicillin and miconazole) with inhibition zones averages of 24.33 ± 0.12, 15.67 ± 0.03, and 17.5 ± 0.49 mm, respectively. The MIC values of the prepared nanocomposite against B. cereus, E. coli, and C. albicans were 80, 80, and 90 µg/ml compared to standard drugs (90, 120 and 150 µg/ml, respectively). According to the TEM ultrastructure studies of nanocomposite-treated microbes, treated cells had severe deformities and morphological alterations compared to the untreated cells including cell wall distortion, the separation between the cell wall and plasma membrane, vacuoles formation moreover complete cell lyses were also noted. In the cytotoxicity test of CS/GO/ZnO alone and its cryogel, there was a significant reduction (pË0.05) in cell viability of WI-38 normal lung cell line after the concentration of 209 and 164 µg/ml, respectively. It showed the low toxic effect of the nanocomposite and its cryogel on the WI-38 line which implies its safety. In addition, water treatment with the CS/GO/ZnO cryogel decreased turbidity (0.58 NTU), total coliform (2 CFU/100 ml), fecal coliform (1 CFU/100 ml), fecal Streptococcus (2 CFU/100 ml), and heterotrophic plate counts (53 CFU/1 ml) not only in comparison with the chlorine-treated samples (1.69 NTU, 4 CFU/100 ml, 6 CFU/100 ml, 57 CFU/100 ml, and 140 CFU/1 ml, respectively) but also with the raw water samples (6.9 NTU, 10800 CFU/100 ml, 660 CFU/100 ml, 800 CFU/100 ml, and 4400 CFU/1 ml, respectively). Moreover, cryogel significantly decreased the concentration of different heavy metals, especially cobalt compared to chlorine (0.004 ppm, 0.002 ppm, and 0.001 ppm for raw water, chlorine-treated, and cryogel-treated groups, respectively) which helped in the reduction of their toxic effects. CONCLUSION: This study provides an effective, promising, safe, and alternative nanocomposite to treat different human and animal pathogenic microbes that might be used in different environmental, industrial, and medical applications.
Assuntos
Bacillus subtilis , Quitosana , Criogéis , Grafite , Nanocompostos , Óxido de Zinco , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Óxido de Zinco/metabolismo , Nanocompostos/química , Bacillus subtilis/metabolismo , Bacillus subtilis/efeitos dos fármacos , Criogéis/química , Quitosana/química , Quitosana/farmacologia , Quitosana/metabolismo , Grafite/química , Metais Pesados/metabolismo , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/metabolismo , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/químicaRESUMO
Rationale: Alzheimer's disease (AD) is hallmarked by amyloid-ß (Aß) plaques and hyperphosphorylated tau (p-tau) neurofibrillary tangles. While Aß-centric therapies have shown promise, the complex pathology of AD requires a multifaceted therapeutic approach. The weak association between Aß levels and cognitive decline highlights the need for alternative theranostic strategies. Currently, oxidative stress and tau hyperphosphorylation are now recognized as critical pathological events in AD. Thus, therapies that concurrently attenuate oxidative stress damage and inhibit tau pathology hold great potential for AD treatment. Methods: Herein, a multifunctional neuron-targeted nanocomposite is devised to realize dual imaging-guided AD therapy, integrating the inhibition of tau pathology and reactive oxygen species (ROS)-neutralizing biofunctions. The construction of the nanocomposite incorporates polyphenolic antioxidants tannic acid (TA)-based nanoparticles carrying manganese ions (Mn2+) and fluorescent dye IR780 iodide (IR780), coupled with a neuron-specific TPL peptide. The resulting IR780-Mn@TA-TPL nanoparticles (NPs) are comprehensively evaluated in both in vitro and in vivo AD models to assess their imaging capabilities and therapeutic efficacy. Results: The nanocomposite facilitates Mn-enhanced magnetic resonance (MR) imaging and near-infrared (NIR) fluorescence imaging. It effectively neutralizes toxic ROS and reduces tau hyperphosphorylation and aggregation. In AD rat models, the nanocomposite restores neuronal density in the hippocampus and significantly improves spatial memory. Conclusions: Such a neurontargeting multifunctional nanocomposite represents a potential theranostic strategy for AD, signifying a shift towards bimodal imaging-guided treatment approaches.
Assuntos
Doença de Alzheimer , Imageamento por Ressonância Magnética , Nanocompostos , Taninos , Proteínas tau , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/diagnóstico por imagem , Animais , Taninos/farmacologia , Taninos/uso terapêutico , Taninos/química , Nanocompostos/química , Imageamento por Ressonância Magnética/métodos , Proteínas tau/metabolismo , Humanos , Ratos , Modelos Animais de Doenças , Imagem Óptica/métodos , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Manganês/química , Nanomedicina Teranóstica/métodos , Terapia Combinada/métodos , PolifenóisRESUMO
This study reports the facile hydrothermal synthesis of pure Bi2WO6 and Bi2WO6\MWCNTs nanocomposite at specific molar ratio 1:2.5 of Bi2WO6:MWCNTs and elucidates their role in modulating the NLRP3 inflammasome pathway via autophagy induction. Comprehensive characterization techniques, including XRD, Raman, UV.Vis PL,FESEM,EDS and TEM, revealed the successful incorporation of MWCNTs into the Bi2WO6 structures, leading to enhanced crystattlinity, reduced band gap energy (2.4 eV) suppressed charge carrier recombination and mitigated nanoparticles aggregation. Notably, the reduced band gap facikitaed improved visible light harvesting, a crucial attribute for photocatalytic applications. Significantly, the nanocompsoite exhibited a remarkable capacity to augment autophagy in bone marrow-derived macrophages (BMDMs), consequently down-regulating the NLRP3 inflammasom activation and IL-1ß secretion upon LPS and ATP stimulation. Immunofluorescence assays unveiled increased co-localization of LC3 and NLRP3, suggestion enhanced targeting of NLRP3 by autophagy. Inhibition of autophagy by 3-MA reversed these effects, confirming the pivotal role of autophagy induction. Furthermore, the nanocomposite attenuated caspase-1 activation and ASC oligomerzation, thereby impeding inflammasome assembly. Collectively, these findings underscore the potential of Bi2WO6\MWCNTs nanocompsite as a multifaceted therapeutic platform, levering its tailored optoelectronic properties and sbility to modulate the NLRP3 infalmmasome via autophagy augmentation. This work covers the way for the development of advanced nanomaterials with tunable functionalities for combating inflammatory disorders and antimicrobial applications.
Assuntos
Autofagia , Inflamassomos , Interleucina-1beta , Proteína 3 que Contém Domínio de Pirina da Família NLR , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Autofagia/efeitos dos fármacos , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Animais , Camundongos , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Nanopartículas/química , Compostos de Tungstênio/farmacologia , Compostos de Tungstênio/química , Caspase 1/metabolismo , Nanocompostos/químicaRESUMO
Preclinical studies demonstrating high cure rates with PD1/PD-L1 combinations have led to numerous clinical trials, but emerging results are disappointing. These combined immunotherapies are commonly employed for patients with refractory tumors following prior treatment with cytotoxic agents. Here, we uncovered that the post-chemotherapy tumor presents a unique mechanical microenvironment characterized by an altered extracellular matrix (ECM) elasticity and increased stiffness, which facilitate the development of aggressive tumor phenotypes and confer resistance to checkpoint blocking therapy. As thus, we rationally designed an in situ nanocomposite hydrogel system, LOS&FeOX@Gel, which enabled effective and specific delivery of the therapeutic payloads (losartan [LOS] and oxaliplatin [OX]) into tumor. We demonstrate that sustained release of LOS effectively remodels the tumor mechanical microenvironment (TMM) by reducing ECM deposition and its associated "solid stress", thereby augmenting the efficacy of OX and its immunological effects. Importantly, this hydrogel system greatly sensitized post-chemotherapy tumor to checkpoint blocking therapy, showing synergistic therapeutic effects against cancer metastasis. Our study provides mechanistic insights and preclinical rationale for modulating TMM as a potential neoadjuvant regimen for tumor to optimize the benefits of chemo-immunotherapy, which lays the groundwork for leveraging "mechanical-immunoengineering" strategies to combat refractory tumors.
Assuntos
Hidrogéis , Imunoterapia , Losartan , Nanocompostos , Microambiente Tumoral , Microambiente Tumoral/efeitos dos fármacos , Animais , Nanocompostos/química , Hidrogéis/química , Camundongos , Imunoterapia/métodos , Linhagem Celular Tumoral , Losartan/farmacologia , Losartan/química , Matriz Extracelular/metabolismo , Humanos , Oxaliplatina/farmacologia , Oxaliplatina/química , Oxaliplatina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Antineoplásicos/farmacologia , Antineoplásicos/química , Camundongos Endogâmicos C57BLRESUMO
Silver nanoparticles-loaded hydrogel nanocomposites are exploited for medicinal and pharmaceutical applications. Hydrogel nanocomposites were prepared from acrylamide (Am), chitosan (CS) and AgNO3 utilizing gamma rays. Diverse variables were applied in preparation of silver nanoparticles-laoded hydrogel nanocomposites of (PAm/CS)-AgNPs such as influence of radiation dose and influnece of CS concentration. Diverse techniques were utilized to characterize hydrogel nanocomposites; Fourier transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), X-ray diffraction (XRD), Transmission electron microscopy (TEM), energy dispersive X-ray (EDX) and scanning electron microscopy (SEM). Results confirmed formation of silver nanoparticles-loaded hydrogel nanocomposites of (PAm/CS)-AgNPs. Antifungal activity of (PAm/CS)-AgNPs hydrogel nanocomposites on viability of C. albicans was esitmated. Results displayed the efficient microbial inhibition activity of treatment against C. albicans compared to control. Furthermore, (PAm/CS)-AgNPs hydrogel nanocomposite against cervical cancer HeLa cell line was investigated. Cytotoxicity of (PAm/CS)-AgNPs hydrogel nanocomposites on prior cancer cell line empolyed to prohibition of cell growth assesssed by MTT test. HeLa cancer cell is treated by (PAm/CS)-AgNPs for 48 h exposed a potential apoptotic activity by noticeable up-regulation of p53 gene expression. Moreover, anticancer activity was investigated by down-regulation of platelet-based growth variable receptor beta (PDGFR-ß), Bcl2, Cathepsine, and MMP-2 gene expression. antioxidant activity was investigated and results showed antioxidant activity of (PAm/CS) hydrogel and (PAm/CS)-AgNPs hydrogel nanocomposite are 87.8% and 62.9%, respectively.
Assuntos
Antifúngicos , Antineoplásicos , Candida albicans , Quitosana , Raios gama , Química Verde , Hidrogéis , Nanopartículas Metálicas , Nanocompostos , Prata , Prata/química , Prata/farmacologia , Candida albicans/efeitos dos fármacos , Quitosana/química , Quitosana/farmacologia , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/síntese química , Humanos , Nanopartículas Metálicas/química , Nanocompostos/química , Hidrogéis/química , Hidrogéis/farmacologia , Células HeLa , Química Verde/métodos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Resinas Acrílicas/química , Resinas Acrílicas/farmacologia , Testes de Sensibilidade Microbiana , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
In this study, we report the green preparation of magnetically separable Ag/Fe3O4/rGO nanocomposites using mangrove tree aerial root extract as a stabilising agent. The morphology, size, chemical composition, magnetic property and other characteristic parameters of synthesised Ag/Fe3O4/rGO nanocomposite were determined by analytical techniques like Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and vibrating sample magnetometer (VSM). The results proved that mangrove tree aerial root extract has the ability to reduce Ag+ ions, graphene oxide (GO) to Ag nanoparticle and reduced graphene oxide (rGO), respectively. The prepared Ag/Fe3O4/rGO nanocomposite was used successfully as a prompt catalyst for synthesis of 7-phenyl-6H,7H-benzo[4,5]imidazo[2,1-b]chromeno[4,3-d][1,3]thiazin-6-one derivatives by one-pot multi-component reaction of 4-hydroxycoumarin (10 mmol), 2-mercaptobenzimidazole (10 mmol) and different arylaldehyde (10 mmol) in the presence of ethanol (10 ml) as an eco-benign solvent at reflux condition. By utilising this protocol, we have constructed 7-phenyl-6H,7H-benzo[4,5]imidazo[2,1-b]chromeno[4,3-d][1,3]thiazin-6-one derivatives in good to excellent yield of 80-90%. This synthesis involves the formation of C-C, C-N and C-S bonds. The synthesised organic heterocyclic compounds were examined for the green matrix properties such as atom economy (AE), E-factor and product mass intensity (PMI). This green protocol is of big interest due to employing simple, non-toxic heterogeneous, separable, reusable Ag/Fe3O4/rGO as an eco-safe heterogeneous catalyst and environmentally benign ethanol as a green solvent without the use of any harmful mineral acid and toxic transition metal catalyst.
Assuntos
Grafite , Nanocompostos , Prata , Nanocompostos/química , Grafite/química , Prata/química , Catálise , Extratos Vegetais/química , Raízes de Plantas , Química VerdeRESUMO
This study investigates the fabrication and characterization of electrospun poly (ε-caprolactone)/poly (vinyl pyrrolidone) (PCL/PVP) fibers integrated with a nanocomposite of chitosan, silver nanocrystals, and graphene oxide (ChAgG), aimed at developing advanced wound dressing materials. The ChAgG nanocomposite, recognized for its antimicrobial and biocompatible properties, was incorporated into PCL/PVP fibers through electrospinning techniques. We assessed the resultant fibers' morphological, physicochemical, and mechanical properties, which exhibited significant enhancements in mechanical strength and demonstrated effective antimicrobial activity against common bacterial pathogens. The findings suggest that the PCL/PVP-ChAgG fibers maintain biocompatibility and facilitate controlled therapeutic delivery, positioning them as a promising solution for managing chronic and burn-related wounds. This study underscores the potential of these advanced materials to improve healing outcomes cost-effectively, particularly in settings plagued by high incidences of burn injuries. Further clinical investigations are recommended to explore these innovative fibers' full potential and real-world applicability.
Assuntos
Bandagens , Quitosana , Grafite , Nanocompostos , Poliésteres , Prata , Cicatrização , Nanocompostos/química , Cicatrização/efeitos dos fármacos , Grafite/química , Grafite/farmacologia , Quitosana/química , Prata/química , Prata/farmacologia , Poliésteres/química , Povidona/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Nanopartículas Metálicas/química , Humanos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Queimaduras/tratamento farmacológico , Queimaduras/terapia , Nanofibras/química , Testes de Sensibilidade MicrobianaRESUMO
Most of published research on magnetic hyperthermia focused on iron oxides, ferrites, and binary alloy nanostructures, while the ternary alloys attracted much limited interest. Herein, we prepared NiCuCo ternary alloy nanocomposites with variable compositions by mechanical alloying. Physical properties were fully characterized by XRD, Rietveld analysis, XPS, SEM/EDX, TEM, ZFC/FC and H-M loops. DFT calculations were used to confirm the experimental results in terms of structure and magnetism. The results showed that the fabricated nanoalloys are face centered cubic (FCC) with average core sizes of 9-40 nm and behave as superparamagnetic with saturation in the range 4.67-42.63 emu/g. Langevin fitting corroborated the superparamagnetic behavior, while law of approach to saturation (LAS) was used to calculate the magnetic anisotropy constants. Heating effciencies were performed under an alternating magnetic field (AMF, H0 = 170 Oe and f = 332.5 kHz), and specific absorption rate (SAR) values were determined. The highest magnetic saturation (Ms), heating potentials, and SAR values were attained for Ni35Cu30Co35 containing the lowest Cu but highest Ni and Co percentages, and the least for Ni15Cu70Co15. Importantly, the nanoalloys reached the required temperatures for magnetic hyperthermia (42 °C) in relatively short times. We also showed that heat dissipiation can be simply tuned by changing many parameters such as concentration, field amplitude, and frequency. Finally, cytotoxicity viability assays against two different breast cancer cell lines treated with Ni25Cu50Co25 nanoalloy in the presence and absence of AMF were investigated. No significant decrease in cancer cell viability was observed in the absence of AMF. When tested against tumorigenic KAIMRC2 breast cancer cells under AMF, the NiCuCo nanoalloy was found to be highly potent to the cells (~ 2-fold enhancement), killing almost all the cells in short times (20 min) and clinically-safe AC magnetic fields. These findings strongly suggest that the as-prepared ternary NiCuCo nanoalloys hold great promise for potential magnetically-triggered cancer hyperthermia.
Assuntos
Ligas , Hipertermia Induzida , Níquel , Ligas/química , Hipertermia Induzida/métodos , Humanos , Níquel/química , Campos Magnéticos , Cobre/química , Cobalto/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Nanocompostos/químicaRESUMO
Chitosan grafted with gallic acid (CS-GA), along with CS-GA doped with CeO2 nanoparticles (CS-GA-CeO2) were synthesized as novel environmentally friendly mild steel corrosion inhibitors. The formation of these derivatives was confirmed by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), hydrogen nuclear magnetic resonance spectroscopy (1H NMR), and thermal analysis (TGA). Based on potentiodynamic polarization curves (PDP) measurements, the inhibitors acted primarily as hybrid inhibitors, while following the Langmuir adsorption theory model. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy(XPS) and 3D surface profiles, confirmed that CS-GA-CeO2 adsorbed on the mild steel forming a protective layer thus preventing the invasion of corrosive media. The corrosion protection mechanism of chitosan derivatives was investigated by molecular dynamics simulations. Electrochemical measurements were used to investigate the corrosion inhibition by CS-GA and CS-GA-CeO2 on mild steel in a 3.5 % NaCl solution. At room temperature, the highest inhibition efficiency (93.58 %) was achieved at 200 ppm CS-GA-CeO2. Modified chitosan nanocomposites were confirmed as promising corrosion inhibitors.
Assuntos
Cério , Quitosana , Ácido Gálico , Nanocompostos , Aço , Cério/química , Aço/química , Nanocompostos/química , Ácido Gálico/química , Corrosão , Quitosana/química , Simulação de Dinâmica Molecular , AdsorçãoRESUMO
Exosomes, extracellular vesicles (EVs) with an average size of 50-150 nm, transfer various biomolecules and exchange signaling molecules between cells in a paracrine manner. Molecular investigations have revealed that EVs can reflect real-time metabolic changes in normal- and cancer-origin cells and thus harbor valid diagnostic biomarkers. Despite these advantages, the detection of low concentrations of cancer cell EVs in biological fluids is still a great challenge. Here, a new electrochemical Exosensor based on platinum-perovskite is developed for the direct detection of EVs using a biotinylated monoclonal CD63 antibody as a capture element. The label-free method exhibited higher sensitivity with a lower limit of quantification of 2000 EVs/µL with a dynamic linear range (LDR) of 2000 to 14,000 EVs/µL compared with other available methods. To enhance the selectivity of detection, EVs were simultaneously sandwiched between secondary antibodies of PSA (prostate-specific antigen), as an FDA-approved prostate cancer biomarker. Data indicated that this Exosensor can distinguish normal and cancer EVs in samples from healthy individuals and prostate cancer patients. Taken together, this technology offers a unique approach to label-free quantification of EVs and cancer detection in the early stages.