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1.
Sci Rep ; 14(1): 10484, 2024 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714767

RESUMO

The current research aimed to study the green synthesis of silver oxide nanoparticles (AgONPs) using Rhynchosia capitata (RC) aqueous extract as a potent reducing and stabilizing agent. The obtained RC-AgONPs were characterized using UV, FT-IR, XRD, DLS, SEM, and EDX to investigate the morphology, size, and elemental composition. The size of the RC-AgONPs was found to be ~ 21.66 nm and an almost uniform distribution was executed by XRD analysis. In vitro studies were performed to reveal biological potential. The AgONPs exhibited efficient DPPH free radical scavenging potential (71.3%), reducing power (63.8 ± 1.77%), and total antioxidant capacity (88.5 ± 4.8%) to estimate their antioxidative power. Antibacterial and antifungal potentials were evaluated using the disc diffusion method against various bacterial and fungal strains, and the zones of inhibition (ZOI) were determined. A brine shrimp cytotoxicity assay was conducted to measure the cytotoxicity potential (LC50: 2.26 µg/mL). In addition, biocompatibility tests were performed to evaluate the biocompatible nature of RC-AgONPs using red blood cells, HEK, and VERO cell lines (< 200 µg/mL). An alpha-amylase inhibition assay was carried out with 67.6% inhibition. Moreover, In vitro, anticancer activity was performed against Hep-2 liver cancer cell lines, and an LC50 value of 45.94 µg/mL was achieved. Overall, the present study has demonstrated that the utilization of R. capitata extract for the biosynthesis of AgONPs offers a cost-effective, eco-friendly, and forthright alternative to traditional approaches for silver nanoparticle synthesis. The RC-AgONPs obtained exhibited significant bioactive properties, positioning them as promising candidates for diverse applications in the spheres of medicine and beyond.


Assuntos
Nanopartículas Metálicas , Compostos de Prata , Nanopartículas Metálicas/química , Animais , Humanos , Compostos de Prata/química , Compostos de Prata/farmacologia , Antioxidantes/farmacologia , Antioxidantes/química , Artemia/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Química Verde/métodos , Antibacterianos/farmacologia , Antibacterianos/química , Testes de Sensibilidade Microbiana , Células Vero , Antifúngicos/farmacologia , Antifúngicos/química , Prata/química , Prata/farmacologia , Óxidos
2.
J Nanobiotechnology ; 22(1): 230, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720322

RESUMO

Tumor vaccines, a crucial immunotherapy, have gained growing interest because of their unique capability to initiate precise anti-tumor immune responses and establish enduring immune memory. Injected tumor vaccines passively diffuse to the adjacent draining lymph nodes, where the residing antigen-presenting cells capture and present tumor antigens to T cells. This process represents the initial phase of the immune response to the tumor vaccines and constitutes a pivotal determinant of their effectiveness. Nevertheless, the granularity paradox, arising from the different requirements between the passive targeting delivery of tumor vaccines to lymph nodes and the uptake by antigen-presenting cells, diminishes the efficacy of lymph node-targeting tumor vaccines. This study addressed this challenge by employing a vaccine formulation with a tunable, controlled particle size. Manganese dioxide (MnO2) nanoparticles were synthesized, loaded with ovalbumin (OVA), and modified with A50 or T20 DNA single strands to obtain MnO2/OVA/A50 and MnO2/OVA/T20, respectively. Administering the vaccines sequentially, upon reaching the lymph nodes, the two vaccines converge and simultaneously aggregate into MnO2/OVA/A50-T20 particles through base pairing. This process enhances both vaccine uptake and antigen delivery. In vitro and in vivo studies demonstrated that, the combined vaccine, comprising MnO2/OVA/A50 and MnO2/OVA/T20, exhibited robust immunization effects and remarkable anti-tumor efficacy in the melanoma animal models. The strategy of controlling tumor vaccine size and consequently improving tumor antigen presentation efficiency and vaccine efficacy via the DNA base-pairing principle, provides novel concepts for the development of efficient tumor vaccines.


Assuntos
Vacinas Anticâncer , Linfonodos , Compostos de Manganês , Camundongos Endogâmicos C57BL , Nanopartículas , Ovalbumina , Óxidos , Animais , Vacinas Anticâncer/imunologia , Linfonodos/imunologia , Camundongos , Ovalbumina/imunologia , Ovalbumina/química , Óxidos/química , Nanopartículas/química , Compostos de Manganês/química , Imunidade Celular , Feminino , Linhagem Celular Tumoral , DNA/química , DNA/imunologia , Imunoterapia/métodos , Melanoma Experimental/imunologia , Melanoma Experimental/terapia , Tamanho da Partícula , Antígenos de Neoplasias/imunologia
3.
Biomed Mater ; 19(4)2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38697132

RESUMO

During the process of malignant tumor treatment, photodynamic therapy (PDT) exerts poor efficacy due to the hypoxic environment of the tumor cells, and long-time chemotherapy reduces the sensitivity of tumor cells to chemotherapy drugs due to the presence of drug-resistant proteins on the cell membranes for drug outward transportation. Therefore, we reported a nano platform based on mesoporous silica coated with polydopamine (MSN@PDA) loading PDT enhancer MnO2, photosensitizer indocyanine green (ICG) and chemotherapeutic drug doxorubicin (DOX) (designated as DMPIM) to achieve a sequential release of different drugs to enhance treatment of malignant tumors. MSN was first synthesized by a template method, then DOX was loaded into the mesoporous channels of MSN, and locked by the PDA coating. Next, ICG was modified by π-π stacking on PDA, and finally, MnO2layer was accumulated on the surface of DOX@MSN@PDA- ICG@MnO2, achieving orthogonal loading and sequential release of different drugs. DMPIM first generated oxygen (O2) through the reaction between MnO2and H2O2after entering tumor cells, alleviating the hypoxic environment of tumors and enhancing the PDT effect of sequentially released ICG. Afterwards, ICG reacted with O2in tumor tissue to produce reactive oxygen species, promoting lysosomal escape of drugs and inactivation of p-glycoprotein (p-gp) on tumor cell membranes. DOX loaded in the MSN channels exhibited a delay of approximately 8 h after ICG release to exert the enhanced chemotherapy effect. The drug delivery system achieved effective sequential release and multimodal combination therapy, which achieved ideal therapeutic effects on malignant tumors. This work offers a route to a sequential drug release for advancing the treatment of malignant tumors.


Assuntos
Doxorrubicina , Liberação Controlada de Fármacos , Verde de Indocianina , Indóis , Compostos de Manganês , Óxidos , Fotoquimioterapia , Fármacos Fotossensibilizantes , Polímeros , Fotoquimioterapia/métodos , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/administração & dosagem , Verde de Indocianina/química , Indóis/química , Animais , Compostos de Manganês/química , Humanos , Polímeros/química , Linhagem Celular Tumoral , Óxidos/química , Fármacos Fotossensibilizantes/química , Dióxido de Silício/química , Camundongos , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Neoplasias/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Portadores de Fármacos/química , Porosidade
4.
J Nanobiotechnology ; 22(1): 294, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38807127

RESUMO

BACKGROUND: Ulcerative colitis (UC) is one chronic and relapsing inflammatory bowel disease. Macrophage has been reputed as one trigger for UC. Recently, phosphodiesterase 4 (PDE4) inhibitors, for instance roflumilast, have been regarded as one latent approach to modulating macrophage in UC treatment. Roflumilast can decelerate cyclic adenosine monophosphate (cAMP) degradation, which impedes TNF-α synthesis in macrophage. However, roflumilast is devoid of macrophage-target and consequently causes some unavoidable adverse reactions, which restrict the utilization in UC. RESULTS: Membrane vesicles (MVs) from probiotic Escherichia coli Nissle 1917 (EcN 1917) served as a drug delivery platform for targeting macrophage. As model drugs, roflumilast and MnO2 were encapsulated in MVs (Rof&MnO2@MVs). Roflumilast inhibited cAMP degradation via PDE4 deactivation and MnO2 boosted cAMP generation by activating adenylate cyclase (AC). Compared with roflumilast, co-delivery of roflumilast and MnO2 apparently produced more cAMP and less TNF-α in macrophage. Besides, Rof&MnO2@MVs could ameliorate colitis in mouse model and regulate gut microbe such as mitigating pathogenic Escherichia-Shigella and elevating probiotic Akkermansia. CONCLUSIONS: A probiotic-based nanoparticle was prepared for precise codelivery of roflumilast and MnO2 into macrophage. This biomimetic nanoparticle could synergistically modulate cAMP in macrophage and ameliorate experimental colitis.


Assuntos
Aminopiridinas , Benzamidas , AMP Cíclico , Ciclopropanos , Macrófagos , Compostos de Manganês , Óxidos , Probióticos , Animais , Aminopiridinas/farmacologia , Camundongos , AMP Cíclico/metabolismo , Probióticos/farmacologia , Ciclopropanos/farmacologia , Ciclopropanos/química , Compostos de Manganês/química , Compostos de Manganês/farmacologia , Benzamidas/farmacologia , Benzamidas/química , Óxidos/farmacologia , Óxidos/química , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Inibidores da Fosfodiesterase 4/farmacologia , Inibidores da Fosfodiesterase 4/química , Colite/tratamento farmacológico , Colite/induzido quimicamente , Células RAW 264.7 , Escherichia coli/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Camundongos Endogâmicos C57BL , Masculino , Modelos Animais de Doenças
5.
J Nanobiotechnology ; 22(1): 264, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760771

RESUMO

Glioblastoma (GBM) is the most aggressive primary brain tumor with low survival rate. Currently, temozolomide (TMZ) is the first-line drug for GBM treatment of which efficacy is unfortunately hindered by short circulation time and drug resistance associated to hypoxia and redox tumor microenvironment. Herein, a dual-targeted and multi-responsive nanoplatform is developed by loading TMZ in hollow manganese dioxide nanoparticles functionalized by polydopamine and targeting ligands RAP12 for photothermal and receptor-mediated dual-targeted delivery, respectively. After accumulated in GBM tumor site, the nanoplatform could respond to tumor microenvironment and simultaneously release manganese ion (Mn2+), oxygen (O2) and TMZ. The hypoxia alleviation via O2 production, the redox balance disruption via glutathione consumption and the reactive oxygen species generation, together would down-regulate the expression of O6-methylguanine-DNA methyltransferase under TMZ medication, which is considered as the key to drug resistance. These strategies could synergistically alleviate hypoxia microenvironment and overcome TMZ resistance, further enhancing the anti-tumor effect of chemotherapy/chemodynamic therapy against GBM. Additionally, the released Mn2+ could also be utilized as a magnetic resonance imaging contrast agent for monitoring treatment efficiency. Our study demonstrated that this nanoplatform provides an alternative approach to the challenges including low delivery efficiency and drug resistance of chemotherapeutics, which eventually appears to be a potential avenue in GBM treatment.


Assuntos
Neoplasias Encefálicas , Resistencia a Medicamentos Antineoplásicos , Glioblastoma , Compostos de Manganês , Nanopartículas , Óxidos , Temozolomida , Microambiente Tumoral , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Microambiente Tumoral/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Linhagem Celular Tumoral , Animais , Compostos de Manganês/química , Compostos de Manganês/farmacologia , Nanopartículas/química , Neoplasias Encefálicas/tratamento farmacológico , Óxidos/química , Óxidos/farmacologia , Camundongos , Sistemas de Liberação de Medicamentos/métodos , Indóis/química , Indóis/farmacologia , Polímeros/química , Camundongos Nus , Camundongos Endogâmicos BALB C , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo
6.
BMC Oral Health ; 24(1): 584, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773504

RESUMO

BACKGROUND: Apical surgery with standard retrograde maneuvers may be challenging in certain cases. Simplifying apical surgery to reduce operating time and streamline retrograde manipulation is an emerging need in clinical endodontics. AIM OF THE STUDY: The aim of the study was to compare the bacterial sealing ability of a calcium silicate-based sealer with the single cone technique combined with root end resection only, and calcium silicate-based sealer as a retrograde filling versus MTA retrofilling, and to analyze bacterial viability using confocal laser scanning microscope (CLSM). MATERIALS AND METHODS: In this in vitro experimental study, 50 extracted human maxillary incisor teeth were instrumented and randomly divided into five groups: three experimental groups, a positive control group, and a negative control group (n = 10/group). In the experimental groups, the roots were obturated using the single cone technique (SCT) and a calcium silicate-based sealer. In group 1, the roots were resected 3 mm from the apex with no further retrograde preparation or filling. In groups 2 and 3, the roots were resected, retroprepared, and retrofilled with either a calcium silicate-based sealer or MTA, respectively. Group 4 (positive control) was filled with a single gutta-percha cone without any sealer. In group 5 (negative control), the canals were left empty, and the roots were sealed with wax and nail varnish. A bacterial leakage model using Enterococcus faecalis was employed to assess the sealing ability over a 30-day period, checking for turbidity and analyzing colony forming units (CFUs) per milliliter. Five specimens from each group were examined using CLSM for bacterial viability. Data for the bacterial sealing ability were statistically analyzed using chi-squared and Kruskal-Wallis tests. RESULTS: The three experimental groups did not show significant differences in terms of bacterial leakage, or bacterial counts (CFUs) (P > 0.05). However, significant differences were observed when comparing the experimental groups to the positive control group. Notably, the calcium silicate-based sealer, when used as a retrofilling, yielded the best sealing ability. CLSM imaging revealed viable bacterial penetration in all the positive control group specimens while for the experimental groups, dead bacteria was the prominent feature seen. CONCLUSION: Within the limitations of this study, it could be concluded that the bacterial sealing ability of calcium silicate-based sealer with the single cone technique combined with root end resection only and calcium silicate-based sealer as a retrograde filling were comparable with MTA retrofilling during endodontic surgical procedures.


Assuntos
Compostos de Cálcio , Materiais Restauradores do Canal Radicular , Silicatos , Silicatos/uso terapêutico , Compostos de Cálcio/uso terapêutico , Humanos , Materiais Restauradores do Canal Radicular/farmacologia , Materiais Restauradores do Canal Radicular/uso terapêutico , Óxidos/farmacologia , Óxidos/uso terapêutico , Combinação de Medicamentos , Compostos de Alumínio/uso terapêutico , Técnicas In Vitro , Microscopia Confocal , Infiltração Dentária/microbiologia , Obturação Retrógrada/métodos , Enterococcus faecalis/efeitos dos fármacos , Viabilidade Microbiana , Incisivo , Apicectomia/métodos
7.
World J Urol ; 42(1): 302, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720010

RESUMO

PURPOSE: To evaluate the diagnostic performance of contrast-enhanced (CE) ultrasound using Sonazoid (SNZ-CEUS) by comparing with contrast-enhanced computed tomography (CE-CT) and contrast-enhanced magnetic resonance imaging (CE-MRI) for differentiating benign and malignant renal masses. MATERIALS AND METHODS: 306 consecutive patients (from 7 centers) with renal masses (40 benign tumors, 266 malignant tumors) diagnosed by both SNZ-CEUS, CE-CT or CE-MRI were enrolled between September 2020 and February 2021. The examinations were performed within 7 days, but the sequence was not fixed. Histologic results were available for 301 of 306 (98.37%) lesions and 5 lesions were considered benign after at least 2 year follow-up without change in size and image characteristics. The diagnostic performances were evaluated by sensitivity, specificity, positive predictive value, negative predictive value, and compared by McNemar's test. RESULTS: In the head-to-head comparison, SNZ-CEUS and CE-MRI had comparable sensitivity (95.60 vs. 94.51%, P = 0.997), specificity (65.22 vs. 73.91%, P = 0.752), positive predictive value (91.58 vs. 93.48%) and negative predictive value (78.95 vs. 77.27%); SNZ-CEUS and CE-CT showed similar sensitivity (97.31 vs. 96.24%, P = 0.724); however, SNZ-CEUS had relatively lower than specificity than CE-CT (59.09 vs. 68.18%, P = 0.683). For nodules > 4 cm, CE-MRI demonstrated higher specificity than SNZ-CEUS (90.91 vs. 72.73%, P = 0.617) without compromise the sensitivity. CONCLUSIONS: SNZ-CEUS, CE-CT, and CE-MRI demonstrate desirable and comparable sensitivity for the differentiation of renal mass. However, the specificity of all three imaging modalities is not satisfactory. SNZ-CEUS may be a suitable alternative modality for patients with renal dysfunction and those allergic to gadolinium or iodine-based agents.


Assuntos
Meios de Contraste , Compostos Férricos , Ferro , Neoplasias Renais , Imageamento por Ressonância Magnética , Óxidos , Tomografia Computadorizada por Raios X , Ultrassonografia , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Ultrassonografia/métodos , Tomografia Computadorizada por Raios X/métodos , Imageamento por Ressonância Magnética/métodos , Idoso , Diagnóstico Diferencial , Adulto , Idoso de 80 Anos ou mais
8.
J Nanobiotechnology ; 22(1): 234, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724978

RESUMO

Radiotherapy-induced immune activation holds great promise for optimizing cancer treatment efficacy. Here, we describe a clinically used radiosensitizer hafnium oxide (HfO2) that was core coated with a MnO2 shell followed by a glucose oxidase (GOx) doping nanoplatform (HfO2@MnO2@GOx, HMG) to trigger ferroptosis adjuvant effects by glutathione depletion and reactive oxygen species production. This ferroptosis cascade potentiation further sensitized radiotherapy by enhancing DNA damage in 4T1 breast cancer tumor cells. The combination of HMG nanoparticles and radiotherapy effectively activated the damaged DNA and Mn2+-mediated cGAS-STING immune pathway in vitro and in vivo. This process had significant inhibitory effects on cancer progression and initiating an anticancer systemic immune response to prevent distant tumor recurrence and achieve long-lasting tumor suppression of both primary and distant tumors. Furthermore, the as-prepared HMG nanoparticles "turned on" spectral computed tomography (CT)/magnetic resonance dual-modality imaging signals, and demonstrated favorable contrast enhancement capabilities activated by under the GSH tumor microenvironment. This result highlighted the potential of nanoparticles as a theranostic nanoplatform for achieving molecular imaging guided tumor radiotherapy sensitization induced by synergistic immunotherapy.


Assuntos
Ferroptose , Imunoterapia , Compostos de Manganês , Proteínas de Membrana , Camundongos Endogâmicos BALB C , Nanopartículas , Nucleotidiltransferases , Óxidos , Radiossensibilizantes , Animais , Camundongos , Imunoterapia/métodos , Óxidos/química , Óxidos/farmacologia , Feminino , Nucleotidiltransferases/metabolismo , Compostos de Manganês/química , Compostos de Manganês/farmacologia , Linhagem Celular Tumoral , Nanopartículas/química , Radiossensibilizantes/farmacologia , Radiossensibilizantes/química , Proteínas de Membrana/metabolismo , Ferroptose/efeitos dos fármacos , Glucose Oxidase/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Humanos , Dano ao DNA , Microambiente Tumoral/efeitos dos fármacos
9.
PLoS One ; 19(5): e0302701, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38728286

RESUMO

Although the toxicity of arsenic depends on its chemical forms, few studies have taken into account the ambiguous phenomenon that sodium arsenite (NaAsO2) acts as a potent carcinogen while arsenic trioxide (ATO, As2O3) serves as an effective therapeutic agent in lymphoma, suggesting that NaAsO2 and As2O3 may act via paradoxical ways to either promote or inhibit cancer pathogenesis. Here, we compared the cellular response of the two arsenical compounds, NaAsO2 and As2O3, on the Burkitt lymphoma cell model, the Epstein Barr Virus (EBV)-positive P3HR1 cells. Using flow cytometry and biochemistry analyses, we showed that a NaAsO2 treatment induces P3HR1 cell death, combined with drastic drops in ΔΨm, NAD(P)H and ATP levels. In contrast, As2O3-treated cells resist to cell death, with a moderate reduction of ΔΨm, NAD(P)H and ATP. While both compounds block cells in G2/M and affect their protein carbonylation and lipid peroxidation, As2O3 induces a milder increase in superoxide anions and H2O2 than NaAsO2, associated to a milder inhibition of antioxidant defenses. By electron microscopy, RT-qPCR and image cytometry analyses, we showed that As2O3-treated cells display an overall autophagic response, combined with mitophagy and an unfolded protein response, characteristics that were not observed following a NaAsO2 treatment. As previous works showed that As2O3 reactivates EBV in P3HR1 cells, we treated the EBV- Ramos-1 cells and showed that autophagy was not induced in these EBV- cells upon As2O3 treatment suggesting that the boost of autophagy observed in As2O3-treated P3HR1 cells could be due to the presence of EBV in these cells. Overall, our results suggest that As2O3 is an autophagic inducer which action is enhanced when EBV is present in the cells, in contrast to NaAsO2, which induces cell death. That's why As2O3 is combined with other chemicals, as all-trans retinoic acid, to better target cancer cells in therapeutic treatments.


Assuntos
Trióxido de Arsênio , Arsenicais , Arsenitos , Autofagia , Mitocôndrias , Estresse Oxidativo , Óxidos , Compostos de Sódio , Trióxido de Arsênio/farmacologia , Arsenitos/farmacologia , Arsenitos/toxicidade , Humanos , Estresse Oxidativo/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Compostos de Sódio/farmacologia , Arsenicais/farmacologia , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Óxidos/farmacologia , Morte Celular/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Herpesvirus Humano 4/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Peróxido de Hidrogênio/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Linfoma de Burkitt/virologia , Linfoma de Burkitt/metabolismo , Linfoma de Burkitt/patologia , Linfoma de Burkitt/tratamento farmacológico
10.
Anal Chim Acta ; 1308: 342664, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38740454

RESUMO

Nanozymes is a kind of nanomaterials with enzyme catalytic properties. Compared with natural enzymes, nanozymes merge the advantages of both nanomaterials and natural enzymes, which is highly important in applications such as biosensing, clinical diagnosis, and food inspection. In this study, we prepared ß-MnOOH hexagonal nanoflakes with a high oxygen vacancy ratio by utilizing SeO2 as a sacrificial agent. The defect-rich MnOOH hexagonal nanoflakes demonstrated excellent oxidase-like activity, catalyzing the oxidation substrate in the presence of O2, thereby rapidly triggering a color reaction. Consequently, a colorimetric sensing platform was constructed to assess the total antioxidant capacity in commercial beverages. The strategy of introducing defects in situ holds great significance for the synthesis of a series of high-performance metal oxide nanozymes, driving the development of faster and more efficient biosensing and analysis methods.


Assuntos
Antioxidantes , Compostos de Manganês , Óxidos , Óxidos/química , Antioxidantes/química , Antioxidantes/metabolismo , Antioxidantes/análise , Compostos de Manganês/química , Colorimetria , Oxirredutases/química , Oxirredutases/metabolismo , Oxirredução , Nanoestruturas/química , Catálise
11.
ACS Appl Mater Interfaces ; 16(19): 24384-24397, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38709640

RESUMO

Vascularization and inflammation management are essential for successful bone regeneration during the healing process of large bone defects assisted by artificial implants/fillers. Therefore, this study is devoted to the optimization of the osteogenic microenvironment for accelerated bone healing through rapid neovascularization and appropriate inflammation inhibition that were achieved by applying a tantalum oxide (TaO)-based nanoplatform carrying functional substances at the bone defect. Specifically, TaO mesoporous nanospheres were first constructed and then modified by functionalized metal ions (Mg2+) with the following deferoxamine (DFO) loading to obtain the final product simplified as DFO-Mg-TaO. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed that the product was homogeneously dispersed hollow nanospheres with large specific surface areas and mesoporous shells suitable for loading Mg2+ and DFO. The biological assessments indicated that DFO-Mg-TaO could enhance the adhesion, proliferation, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). The DFO released from DFO-Mg-TaO promoted angiogenetic activity by upregulating the expressions of hypoxia-inducible factor-1 (HIF-1α) and vascular endothelial growth factor (VEGF). Notably, DFO-Mg-TaO also displayed anti-inflammatory activity by reducing the expressions of pro-inflammatory factors, benefiting from the release of bioactive Mg2+. In vivo experiments demonstrated that DFO-Mg-TaO integrated with vascular regenerative, anti-inflammatory, and osteogenic activities significantly accelerated the reconstruction of bone defects. Our findings suggest that the optimized DFO-Mg-TaO nanospheres are promising as multifunctional fillers to speed up the bone healing process.


Assuntos
Regeneração Óssea , Desferroxamina , Magnésio , Células-Tronco Mesenquimais , Óxidos , Tantálio , Desferroxamina/química , Desferroxamina/farmacologia , Regeneração Óssea/efeitos dos fármacos , Tantálio/química , Animais , Óxidos/química , Óxidos/farmacologia , Magnésio/química , Magnésio/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Osteogênese/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Ratos , Camundongos , Ratos Sprague-Dawley , Proliferação de Células/efeitos dos fármacos , Angiogênese
12.
ACS Appl Mater Interfaces ; 16(20): 25879-25891, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38718301

RESUMO

Biological imaging-guided targeted tumor therapy has been a soughtafter goal in the field of cancer diagnosis and treatment. To this end, we proposed a strategy to modulate surface plasmon resonance and endow WO3-x nanoparticles (NPs) with enzyme-like catalytic properties by doping Fe2+ in the structure of the NPs. Doping of the Fe2+ introduced oxygen vacancies into the structure of the NPs, inducing a red shift of the maximum absorption wavelength into the near-infrared II (NIR-II) region and enhancing the photoacoustic (PA) and photothermal properties of the NPs for more effective imaging-guided cancer therapy. Under NIR-II laser irradiation, the Fe-WO3-x NPs produced very strong NIR-II PA and photothermal effects, which significantly enhanced the PA imaging and photothermal treatment effects. On the other hand, Fe2+ in Fe-WO3-x could undergo Fenton reactions with H2O2 in the tumor tissue to generate ·OH for chemodynamic therapy. In addition, Fe-WO3-x can also catalyze the above reactions to produce more reactive oxygen species (ROS) and induce the oxidation of NADH to interfere with intracellular adenosine triphosphate (ATP) synthesis, thereby further improving the efficiency of cancer therapy. Specific imaging of tumor tissue and targeted synergistic therapy was achieved after ligation of a MUC1 aptamer to the surface of the Fe-WO3-x NPs by the complexing of -COOH in MUC1 with tungsten ions on the surface of the NPs. These results demonstrated that Fe-WO3-x NPs could be a promising diagnosis and therapeutic agent for cancer. Such a study opens up new avenues into the rational design of nanodiagnosis and treatment agents for NIR-II PA imaging and cancer therapy.


Assuntos
Técnicas Fotoacústicas , Ressonância de Plasmônio de Superfície , Tungstênio , Animais , Humanos , Camundongos , Tungstênio/química , Raios Infravermelhos , Óxidos/química , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Nanopartículas/química , Nanopartículas/uso terapêutico , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo
13.
PLoS One ; 19(5): e0304352, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38787832

RESUMO

PURPOSE: To evaluate the added value of contrast-enhanced ultrasonography (CEUS) using Sonazoid in characterizing focal liver lesions (FLLs) with indeterminate findings on gadoxetic acid-enhanced liver MRI in patients without risk factors for hepatocellular carcinoma (HCC). METHODS: Patients who underwent CEUS using Sonazoid for characterizing indeterminate FLLs on gadoxetic acid-enhanced liver MRI were. The indeterminate FLLs were classified according to the degree of malignancy on a 5-point scale on MRI and combined MRI and CEUS. The final diagnosis was made either pathologically or based on more than one-year follow-up. The diagnostic performance was assessed using a receiver operating characteristic (ROC) curve analysis, and the net reclassification improvement (NRI) was calculated. RESULTS: A total of 97 patients (mean age, 49 years ± 16, 41 men, 80 benign and 17 malignant lesions) were included. When CEUS was added to MRI, the area under the ROC curve increased, but the difference was not statistically significant (0.87 [95% confidence interval {CI}, 0.77-0.98] for MRI vs 0.93 [95% CI, 0.87-0.99] for CEUS added to MRI, P = 0.296). The overall NRI was 0.473 (95% CI, 0.100-0.845; P = 0.013): 33.8% (27/80) of benign lesions and 41.2% (7/17) of malignant lesions were appropriately reclassified, whereas 10.0% (8/80) of benign lesions and 17.6% (3/17) of malignant lesions were incorrectly reclassified. CONCLUSIONS: Although performing CEUS with Sonazoid did not significantly improve the overall diagnostic performance in characterizing indeterminate FLLs on gadoxetic acid-enhanced liver MRI in patients without risk factors for HCC, it may increase radiologist's confidence in classifying FLLs.


Assuntos
Carcinoma Hepatocelular , Meios de Contraste , Compostos Férricos , Gadolínio DTPA , Ferro , Neoplasias Hepáticas , Imageamento por Ressonância Magnética , Óxidos , Ultrassonografia , Humanos , Masculino , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Pessoa de Meia-Idade , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Feminino , Imageamento por Ressonância Magnética/métodos , Ultrassonografia/métodos , Adulto , Fatores de Risco , Curva ROC , Idoso , Fígado/diagnóstico por imagem , Fígado/patologia
14.
J Dent Res ; 103(6): 652-661, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38716736

RESUMO

The process of neovascularization during cell-based pulp regeneration is difficult to study. Here we developed a tube model that simulates root canal space and allows direct visualization of the vascularization process in vitro. Endothelial-like cells (ECs) derived from guiding human dental pulp stem cells (DPSCs) into expressing endothelial cell markers CD144, vWF, VEGFR1, and VEGFR2 were used. Human microvascular endothelial cells (hMVECs) were used as a positive control. DPSC-ECs formed tubules on Matrigel similar to hMVECs. Cells were mixed in fibrinogen/thrombin or mouse blood and seeded into wells of 96-well plates or injected into a tapered plastic tube (14 mm in length and 1 or 2 mm diameter of the apex opening) with the larger end sealed with MTA to simulate root canal space. Cells/gels in wells or tubes were incubated for various times in vitro and observed under the microscope for morphological changes. Samples were then fixed and processed for histological analysis to determine vessel formation. Vessel-like networks were observed in culture from 1 to 3 d after cell seeding. Cells/gels in 96-well plates were maintained up to 25 d. Histologically, both hMVECs and DPSC-ECs in 96-well plates or tubes showed intracellular vacuole formation. Some cells showed merged large vacuoles indicating the lumenization. Tubular structures were also observed resembling blood vessels. Cells appeared healthy throughout the tube except some samples (1 mm apical diameter) in the coronal third. Histological analysis also showed pulp-like soft tissue throughout the tube samples with vascular-like structures. hMVECs formed larger vascular lumen size than DPSC-ECs while the latter tended to have more lumen and tubular structure counts. We conclude that DPSC-ECs can form vascular structures and sustained in the 3-dimensional fibrin gel system in vitro. The tube model appears to be a proper and simple system simulating the root canal space for vascular formation and pulp regeneration studies.


Assuntos
Polpa Dentária , Combinação de Medicamentos , Células Endoteliais , Neovascularização Fisiológica , Proteoglicanas , Regeneração , Células-Tronco , Polpa Dentária/citologia , Polpa Dentária/irrigação sanguínea , Polpa Dentária/fisiologia , Neovascularização Fisiológica/fisiologia , Animais , Camundongos , Humanos , Regeneração/fisiologia , Células Endoteliais/fisiologia , Células-Tronco/fisiologia , Colágeno , Técnicas de Cultura de Células , Laminina , Fator de von Willebrand/análise , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Fibrinogênio , Cavidade Pulpar , Compostos de Cálcio , Compostos de Alumínio , Materiais Restauradores do Canal Radicular , Microvasos/citologia , Células Cultivadas , Óxidos , Silicatos , Antígeno CD146
15.
Environ Sci Pollut Res Int ; 31(24): 35678-35687, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38740682

RESUMO

This study effectively addresses the rapid deactivation of manganese-based catalysts in humid environments during ozone decomposition by introducing iron-doped manganese oxide octahedral molecular sieve (Fe-OMS-2) catalysts supported on activated carbon (AC). By optimizing the doping ratio of Fe-OMS-2, the Fe-OMS-20.5/AC catalyst achieves nearly 100% ozone decomposition efficiency across a wide range of relative humidity levels (0 to 60%), even at elevated air flow rates of 800 L·g-1·h-1, outperforming standalone AC, Fe-OMS-2, or a simple mixture of OMS-2 and AC. The Fe-OMS-20.5/AC catalyst features a porous surface and a mesoporous structure, providing a substantial specific surface area that facilitates the uniform distribution of the Fe-OMS-2 active phase on the AC surface. The incorporation of Fe3+ ions enhances electron transfer between valence state transitions of Mn, thereby improving the catalyst's efficiency in ozone decomposition. Additionally, the AC component protects catalytic sites and enhances the catalyst's humidity resistance. In conclusion, this research presents a novel strategy for developing highly efficient and cost-effective ozone decomposition catalysts that enhance dehumidification, significantly contributing to industrial ozone treatment technologies and advancing environmental protection.


Assuntos
Carvão Vegetal , Umidade , Ferro , Ozônio , Ozônio/química , Carvão Vegetal/química , Ferro/química , Catálise , Óxidos/química , Carbono/química , Compostos de Manganês/química
16.
ACS Appl Mater Interfaces ; 16(21): 27187-27201, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38747985

RESUMO

Development of theranostic nanomedicines to tackle glioma remains to be challenging. Here, we present an advanced blood-brain barrier (BBB)-crossing nanovaccine based on cancer cell membrane-camouflaged poly(N-vinylcaprolactam) (PVCL) nanogels (NGs) incorporated with MnO2 and doxorubicin (DOX). We show that the disulfide bond-cross-linked redox-responsive PVCL NGs can be functionalized with dermorphin and imiquimod R837 through cell membrane functionalization. The formed functionalized PVCL NGs having a size of 220 nm are stable, can deplete glutathione, and responsively release both Mn2+ and DOX under the simulated tumor microenvironment to exert the chemo/chemodynamic therapy mediated by DOX and Mn2+, respectively. The combined therapy induces tumor immunogenic cell death to maturate dendritic cells (DCs) and activate tumor-killing T cells. Further, the nanovaccine composed of cancer cell membranes as tumor antigens, R837 as an adjuvant with abilities of DC maturation and macrophages M1 repolarization, and MnO2 with Mn2+-mediated stimulator of interferon gene activation of tumor cells can effectively act on both targets of tumor cells and immune cells. With the dermorphin-mediated BBB crossing, cell membrane-mediated homologous tumor targeting, and Mn2+-facilitated magnetic resonance (MR) imaging property, the designed NG-based theranostic nanovaccine enables MR imaging and combination chemo-, chemodynamic-, and imnune therapy of orthotopic glioma with a significantly decreased recurrence rate.


Assuntos
Glioma , Imageamento por Ressonância Magnética , Compostos de Manganês , Nanomedicina Teranóstica , Glioma/diagnóstico por imagem , Glioma/tratamento farmacológico , Glioma/terapia , Glioma/patologia , Animais , Camundongos , Humanos , Compostos de Manganês/química , Compostos de Manganês/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Vacinas Anticâncer/química , Imunoterapia , Óxidos/química , Óxidos/farmacologia , Linhagem Celular Tumoral , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patologia , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Barreira Hematoencefálica/metabolismo , Nanogéis/química , Imiquimode/química , Imiquimode/farmacologia , Nanovacinas
17.
Anal Chem ; 96(21): 8814-8821, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38751335

RESUMO

Highly responsive interface of semiconductor nanophotoelectrochemical materials provides a broad development prospect for the identification of low-abundance cancer marker molecules. This work innovatively proposes an efficient blank WO3/SnIn4S8 heterojunction interface formed by self-assembly on the working electrode for interface regulation and photoregulation. Different from the traditional biomolecular layered interface, a hydrogel layer containing manganese dioxide with a wide light absorption range is formed at the interface after an accurate response to external immune recognition. The formation of the hydrogel layer hinders the effective contact between the heterojunction interface and the electrolyte solution, and manganese dioxide in the hydrogel layer forms a strong competition between the light source and the substrate photoelectric material. The process effectively improves the carrier recombination efficiency at the interface, reduces the interface reaction kinetics and photoelectric conversion efficiency, and thus provides strong support for target identification. Taking advantage of the process, the resulting biosensors are being explored for sensitive detection of human epidermal growth factor receptor 2, with a limit of detection as low as 0.037 pg/mL. Also, this study contributes to the advancement of photoelectrochemical biosensing technology and opens up new avenues for the development of sensitive and accurate analytical tools in the field of bioanalysis.


Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Compostos de Manganês , Óxidos , Receptor ErbB-2 , Humanos , Técnicas Eletroquímicas/métodos , Óxidos/química , Compostos de Manganês/química , Receptor ErbB-2/imunologia , Receptor ErbB-2/metabolismo , Hidrogéis/química , Processos Fotoquímicos , Limite de Detecção , Eletrodos , Imunoensaio/métodos , Tungstênio/química
18.
Mikrochim Acta ; 191(5): 239, 2024 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-38570399

RESUMO

To accurately detect tumor marker carbohydrate antigen 72-4 (CA72-4) of serum samples is of great significance for the early diagnosis of malignant tumors. In the present study, MnO2/hollow nanobox metal-organic framework (HNM)-AuPtPd nanocomposites were prepared via multi-step synthesis and superposition method and a series of characterizations were carried out. A highly sensitive immunosensor Ab/MnO2/HNM-AuPtPd/GCE based on the composite nanomaterial was further prepared and used to detect the tumor marker CA72-4. The constructed immunosensor achieved signal amplification by increasing the electrocatalytic activity to H2O2 by means of the synergistic effect of MnO2 ultra-thin nanosheets (MnO2 UNs) and HNM-AuPtPd. At the same time, the electrochemical properties of the immunosensor were analyzed using cyclic voltammetry, electrochemical impedance, amperometry (with the test voltage of -0.4 V), and differential pulse voltammetry. The experimental results showed that the MnO2/HNM-AuPtPd nanocomposites were successfully prepared, and the immunosensor Ab/MnO2/HNM-AuPtPd/GCE demonstrated an excellent electrochemical performance. The electrochemical immunosensor had the highest detection sensitivity under the optimal experimental conditions, such as incubation pH of 7.0, incubation time of 60 min, with the addition of 15 µL of H2O2, and in the concentration range 0.001-500 U/mL. It had a low detection limit of 1.78×10-5 U/mL (S/N = 3). Moreover, the serum sample recovery were in the range from 99.38 to 100.52%. This study provides a new method and experimental basis for the detection of tumor markers in clinical practice.


Assuntos
Antígenos Glicosídicos Associados a Tumores , Técnicas Biossensoriais , Nanocompostos , Biomarcadores Tumorais , Técnicas Biossensoriais/métodos , Peróxido de Hidrogênio/química , Compostos de Manganês/química , Óxidos/química , Imunoensaio , Nanocompostos/química
19.
Waste Manag ; 182: 44-54, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38636125

RESUMO

Pyrolysis can effectively convert waste tires into high-value products. However, the sulfur-containing compounds in pyrolysis oil and gas would significantly reduce the environmental and economic feasibility of this technology. Here, the desulfurization and upgrade of waste tire pyrolysis oil and gas were performed by adding different metal oxides (Fe2O3, CuO, and CaO). Results showed that Fe2O3 exhibited the highest removal efficiency of 87.7 % for the sulfur-containing gas at 600 °C with an outstanding removal efficiency of 99.5 % for H2S. CuO and CaO were slightly inferior to Fe2O3, with desulfurization efficiencies of 75.9 % and 45.2 % in the gas when added at 5 %. Fe2O3 also demonstrated a notable efficacy in eliminating benzothiophene, the most abundant sulfur compound in pyrolysis oil, with a removal efficiency of 78.1 %. Molecular dynamics simulations and experiments showed that the desulfurization mechanism of Fe2O3 involved the bonding of Fe-S, the breakage of C-S, dehydrogenation and oxygen migration process, which promoted the conversion of Fe2O3 to FeO, FeS and Fe2(SO4)3. Meanwhile, Fe2O3 enhanced the cyclization and dehydrogenation reaction, facilitating the upgrade of oil and gas (monocyclic aromatics to 57.4 % and H2 to 22.3 %). This study may be helpful for the clean and high-value conversion of waste tires.


Assuntos
Óxidos , Pirólise , Óxidos/química , Enxofre/química , Incineração/métodos , Compostos Férricos/química , Gases/química , Borracha/química , Compostos de Cálcio/química , Cobre
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