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1.
Molecules ; 28(2)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36677854

RESUMO

This study examined the effect of gold nanoparticles (AuNPs) on doxorubicin (DOX)-induced liver damage and steatosis in rats and tested its effect mechanism. Wistar male rats were divided into four groups (each of eight rats) as control, AuNPs (50 µL of 10 nm), DOX (15 mg/kg; 3 mg/kg/week), and DOX + AuNPs-treated rats. DOX is known to induce fasting hyperglycemia and hyperinsulinemia in treated rats. Individual treatment of both DOX and AuNPs also promoted liver damage, increased circulatory levels of ALT and AST, and stimulated serum and liver levels of TGs, CHOL, LDL-c, and FFAs. They also stimulated MDA, TNF-α, and IL-6, reduced GSH, SOD, HO-1, and CAT, upregulated mRNA levels of Bax and caspases-3 and -8 and downregulated mRNA levels of Bcl2 in the livers of rats. However, while DOX alone reduced hepatic levels of PPARα, both AuNPs and DOX stimulated mRNA levels of SREBP1, reduced the mRNA, cytoplasmic and nuclear levels of Nrf2, and increased mRNA, cytoplasmic, and nuclear levels of NF-κB. The liver damage and the alterations in all these parameters were significantly more profound when both AuNPs and DOX were administered together. In conclusion, AuNPs exaggerate liver damage, hyperlipidemia, and hepatic steatosis in DOX-treated rats by activating SREBP1 and NF-κB and suppressing the Nrf2/antioxidant axis.


Assuntos
Fígado Gorduroso , Hiperlipidemias , Nanopartículas Metálicas , Ratos , Masculino , Animais , Ouro/farmacologia , Estresse Oxidativo , Fator 2 Relacionado a NF-E2/metabolismo , Ratos Wistar , NF-kappa B/metabolismo , Hiperlipidemias/induzido quimicamente , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/metabolismo , Fígado , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso/metabolismo , Doxorrubicina/farmacologia
2.
Nanoscale ; 15(4): 1890-1899, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36606731

RESUMO

Dry eye disease (DED), a complex ocular surface disease with a high prevalence rate, is associated with corneal injury, excess oxidative stress and inflammation. Current therapeutic strategies, including artificial tears and anti-inflammatory agents, are unable to address all the deleterious factors or to achieve a clinical cure due to their temporary or side effects. Here, we prepared a multiple-functional eyedrop based on the deposition of gold nanoparticles (AuNPs) reduced by ascorbic acid (AA) onto the exosomal phospholipid membrane of mesenchymal stem cell (mExo)-derived exosomes in situ (mExo@AA). The therapeutic value of mExo@AA for DED was demonstrated in a mouse DED model. Combining the benefits of mExo and AA, mExo@AA effectively improves corneal epithelium recovery and anti-inflammation capacity, decreases corneal reactive oxygen species, and restores tear secretion without adverse effects. Thus, this study suggests that mExo@AA is effective and safe as a therapeutic agent for the treatment of DED.


Assuntos
Síndromes do Olho Seco , Exossomos , Nanopartículas Metálicas , Camundongos , Animais , Ouro/farmacologia , Soluções Oftálmicas , Ácido Ascórbico/farmacologia , Exossomos/metabolismo , Nanopartículas Metálicas/uso terapêutico , Síndromes do Olho Seco/tratamento farmacológico , Anti-Inflamatórios
3.
Int J Mol Sci ; 24(1)2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36614237

RESUMO

This work compared the effectiveness of several Methylene Blue (MB)-based protocols for photo-eradication of biofilms formed on the surface of the glass and stainless steel discs by S. aureus MRSA isolates using a diode laser (λ = 665 nm; output power 40 mW; energy fluence was 189 J cm-2). The results obtained showed that MB alone, up to a concentration of 62.5 mgL-1, had limited photo-bactericidal activity. It was possible to enhance the activity of MB using two types of spherical gold nanoparticles of similar sizes, 15 ± 3 nm/20 ± 3 nm, but differing in the method of their synthesis and stabilization. The enhancement of the photodestruction effect was related to the increased production of hydroxyl radicals by the MB+gold nanoparticles mixture, and this mixture showed dark cytotoxicity against the cocci studied. Effective destruction (mortality above 99.9%) of the biofilms formed by MRSA isolates was also possible without the use of gold nanoparticles, but the concentration of MB had to be at least 125 mgL-1. A highly efficient protocol of photodestruction of biofilms, consisting of triple exposure of biofilms to laser light in the presence of MB alone, combined with the removal of dead bacteria protecting deep layers of pathogens against photosensitization, was also described.


Assuntos
Nanopartículas Metálicas , Staphylococcus aureus Resistente à Meticilina , Fotoquimioterapia , Staphylococcus aureus , Fotoquimioterapia/métodos , Azul de Metileno/farmacologia , Ouro/farmacologia , Biofilmes , Antibacterianos
4.
Molecules ; 28(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36615627

RESUMO

Radiotherapy (RT) is one of the main clinical therapeutic strategies against cancer. Currently, multiple radiosensitizers aimed at enhancing X-ray absorption in cancer tissues have been developed, while limitations still exist for their further applications, such as poor cellular uptake, hypoxia-induced radioresistance, and unavoidable damage to adjacent normal body tissues. In order to address these problems, a cell-penetrating TAT peptide (YGRKKRRQRRRC)-modified nanohybrid was constructed by doping high-Z element Au in hollow semiconductor Cu2-xSe nanoparticles for combined RT and photothermal therapy (PTT) against breast cancer. The obtained Cu2-xSe nanoparticles possessed excellent radiosensitizing properties based on their particular band structures, and high photothermal conversion efficiency beneficial for tumor ablation and promoting RT efficacy. Further doping high-Z element Au deposited more high-energy radiation for better radiosensitizing performance. Conjugation of TAT peptides outside the constructed Cu2-xSe/Au nanoparticles facilitated their cellular uptake, thus reducing overdosage-induced side effects. This prepared multifunctional nanohybrid showed powerful suppression effects towards breast cancer, both in vitro and in vivo via integrating enhanced cell penetration and uptake, and combined RT/PTT strategies.


Assuntos
Neoplasias da Mama , Peptídeos Penetradores de Células , Nanopartículas Metálicas , Neoplasias , Humanos , Feminino , Terapia Fototérmica , Nanopartículas Metálicas/uso terapêutico , Nanopartículas Metálicas/química , Ouro/farmacologia , Ouro/química , Neoplasias da Mama/terapia , Linhagem Celular Tumoral
5.
Nanoscale ; 15(3): 1014-1023, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36602182

RESUMO

Otitis media (OM) is the main cause of pediatric antibiotic prescriptions. Nontypeable Haemophilus influenzae (NTHi) is a major OM pathogen, which forms a biofilm that resists conventional antimicrobials and immune clearance. Thus, novel treatments that are effective against NTHi and its biofilm are urgently required. Nanozymes (often inorganic nanoparticles) mimic natural enzymes' catalytic activities to generate strong antimicrobials at the site of infection, and thus represent one of the emerging solutions to the crisis of antimicrobial resistance. They mimic natural enzymes' activities, such as generating strong antimicrobials catalytically at the site of infection, to minimize overexposure. However, that in situ generation often relies on Reactive Oxygen Species (ROS) as precursors, a prerequisite that limits the broad deployment of nanozymes. To address this challenge, we designed a cascade nanozyme that generates an antiseptic, HOBr, from a ubiquitous non-ROS, i.e., O2, which successfully eradicates NTHi. The cascade nanozyme simultaneously exhibits glucose oxidase (GOx)-like activity from gold nanoparticles (AuNPs) and haloperoxidase (HPO)-mimicking activity from vanadium pentoxide nanowires (V2O5 NWs) connected using dopamine (DPA). The cascade nanozyme demonstrated strong antimicrobial efficacy against NTHi and its biofilm, while showing improved biocompatibility compared to the nanozyme of V2O5 NWs alone. The cascade nanozyme thus points to a material-oriented infectious disease treatment strategy, where small-molecule antimicrobials are generated in real time at the site of infection for the benefit of autonomous dosing. This strategy potentially mitigates the development of antimicrobial resistance and reduces side effects.


Assuntos
Anti-Infecciosos , Nanopartículas Metálicas , Otite Média , Humanos , Criança , Ouro/farmacologia , Haemophilus influenzae , Nanopartículas Metálicas/uso terapêutico , Biofilmes , Anti-Infecciosos/farmacologia
6.
Int J Nanomedicine ; 18: 243-261, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36660336

RESUMO

Purpose: This study aimed to evaluate the radiosensitizing potential of Au@DTDTPA(Gd) nanoparticles when combined with conventional external X-ray irradiation (RT) to treat GBM. Methods: Complementary biological models based on U87 spheroids including conventional 3D invasion assay, organotypic brain slice cultures, chronic cranial window model were implemented to investigate the impact of RT treatments (10 Gy single dose; 5×2 Gy or 2×5 Gy) combined with Au@DTDTPA(Gd) nanoparticles on tumor progression. The main tumor mass and its infiltrative area were analyzed. This work focused on the invading cancer cells after irradiation and their viability, aggressiveness, and recurrence potential were assessed using mitotic catastrophe quantification, MMP secretion analysis and neurosphere assays, respectively. Results: In vitro clonogenic assays showed that Au@DTDTPA(Gd) nanoparticles exerted a radiosensitizing effect on U87 cells, and in vivo experiments suggested a benefit of the combined treatment "RT 2×5 Gy + Au@DTDTPA(Gd)" compared to RT alone. Invasion assays revealed that invasion distance tended to increase after irradiation alone, while the combined treatments were able to significantly reduce tumor invasion. Monitoring of U87-GFP tumor progression using organotypic cultures or intracerebral grafts confirmed the anti-invasive effect of Au@DTDTPA(Gd) on irradiated spheroids. Most importantly, the combination of Au@DTDTPA(Gd) with irradiation drastically reduced the number, the viability and the aggressiveness of tumor cells able to escape from U87 spheroids. Notably, the combined treatments significantly reduced the proportion of escaped cells with stem-like features that could cause recurrence. Conclusion: Combining Au@DTDTPA(Gd) nanoparticles and X-ray radiotherapy appears as an attractive therapeutic strategy to decrease number, viability and aggressiveness of tumor cells that escape and can invade the surrounding brain parenchyma. Hence, Au@DTDTPA(Gd)-enhanced radiotherapy opens up interesting perspectives for glioblastoma treatment.


Assuntos
Glioblastoma , Nanopartículas Metálicas , Humanos , Ouro/farmacologia , Glioblastoma/radioterapia , Gadolínio , Linhagem Celular Tumoral , Nanopartículas Metálicas/uso terapêutico , Meios de Contraste , Quelantes
7.
Chem Commun (Camb) ; 59(9): 1213-1216, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36629520

RESUMO

A lot of attention has been focused on the functionalization of carbohydrate ligands on specific sizes and shapes of gold nanoparticles (AuNPs), where ultrasmall fluorescent AuNPs have not been well explored for direct imaging. Herein, we have engineered fluorescent gold nanoclusters with sulfated oligo-iduronic acid ligands (I34), which strongly bind to the HB-EGF receptor over FGF2, and regulate EGF receptor-mediated cancer cell homing in both two- and three-dimensional (2D and 3D) cell culture systems. These results offer a new practical and direct imaging tool for carbohydrate research.


Assuntos
Nanopartículas Metálicas , Neoplasias , Ouro/farmacologia , Proteínas de Transporte , Corantes , Receptores ErbB , Carboidratos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico
8.
J Mater Chem B ; 11(4): 879-889, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36594928

RESUMO

Although immunotherapy in combination with anti-angiogenesis therapy has made a breakthrough in the first-line treatment of cancer, considering the low responder rate and the adverse events, it is vital to propose a new combination modality. In this study, we report single encapsulated mesoporous silica coated gold nanoparticles that synergize sensitizing radiotherapy with the current combination therapy. Distinguished from simply combining two treatments, the nanoparticle-mediated "trident" therapy resolved the problem of matching the dose between radiation and drug, which determines the outcome since drug demand rises with immunosuppression from increased sensitivity to radiotherapy. The nanomedicine produced energy depositions when radiation was introduced, and released the loaded toripalimab and bevacizumab, exhibiting significant anti-tumor properties. In vitro tumor cell viability results indicated the highest inhibition by the "trident" therapy and in vivo animal models also revealed the earliest decrease in tumor tissue volume. As a result, the "trident" therapy is expected to further improve the anti-tumor benefits of the combination of immunotherapy and anti-angiogenesis therapy and provides a versatile perspective on cancer treatment.


Assuntos
Ouro , Nanopartículas Metálicas , Animais , Ouro/farmacologia , Dióxido de Silício/farmacologia , Sistemas de Liberação de Medicamentos , Imunoterapia
9.
Nanoscale ; 15(3): 1273-1288, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36541678

RESUMO

Photothermal therapy (PTT) has emerged as a very potent therapeutic approach in the treatment of tumors. Gold nanoparticles have gained considerable scientific interest as a photosensitizer due to their absorbance in the near-infrared regions. However, their biodegradation and excretion from the body is a challenge. Various biodegradable systems consisting of liposomes and polymers have been synthesized, but their precise manufacturing and decomposition mechanisms have not yet been explored. Using zein nanoparticles as a template, we have fabricated a glutathione-functionalized gold core shell type of formulation. The scalability of the one-step seedless gold coating process is also reported. The synthesis procedure of these tunable nanoparticles is understood with TEM. The thermal degradation of the material under the physiological conditions is thoroughly examined using UV and TEM. In vitro PTT effectiveness on breast cancer cells is assessed after an extensive in vitro toxicity research. The mechanism of cell death is studied using ROS and cell cycle analysis. The material exhibited good efficacy as a PTT agent in mice and showed non-toxicity up to 14 days. The renal clearance study of the material in mice shows its disintegration into renal clearable minute gold seeds. All the findings suggest biodegradable glutathione-functionalized gold core-shell nanoparticles as potential photothermal cancer treatment agents.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Fotoquimioterapia , Animais , Camundongos , Ouro/farmacologia , Ouro/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fototerapia , Linhagem Celular Tumoral
10.
ACS Biomater Sci Eng ; 9(1): 340-351, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36533725

RESUMO

Combinatorial photothermal therapy and chemotherapy is an extremely promising tumor therapeutic modality. However, such systems still remain challenges in stimulus sensitivity, avoiding drug leakage, and therapeutic safety. To solve these problems, we engineered actively loaded doxorubicin (DOX) and gold nanorod (GNR) liposomes through embedding stiff hollow mesoporous silica nanoparticles (HMSNs) in the liposomal water cavity (HMLGDB) to resist the influence of shear force of GNRs to prevent drug leakage. Under 808 nm laser irradiation, the ambient temperature was raised greatly because of the photothermal conversion of GNRs, thereby rupturing the lipid layer and then triggering the DOX release. The results of in vitro experiments showed that the low concentration of HMLGDB (15 µg/mL) could effectively overcome the MCF-7 cells (human breast cancer cell line) by the increase of DOX concentration intracellularly and the good photothermal effect of GNRs. After intravenous injection, HMLGDB exhibited intratumor aggregation and PTT capacity. Furthermore, the combined chemo-photothermal antitumor strategy demonstrated a high inhibition of tumor growth and low damage to normal tissues. The developed hybrids provide a paradigm for efficient combinatorial photothermal therapy (PTT) and chemotherapy (CT).


Assuntos
Hipertermia Induzida , Nanotubos , Neoplasias , Humanos , Lipossomos , Ouro/farmacologia , Doxorrubicina/farmacologia , Neoplasias/tratamento farmacológico
11.
Bioorg Chem ; 131: 106317, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36525920

RESUMO

Radioresistance represents a common phenomenon found in cancer treatment. Herein, the current study sought to evaluate the effects of a nanodrug delivery system of YSAYPDSVPMMS (YSA) peptide-modified gold nanoparticles-dextran-based hydrogel loaded with paclitaxel-succinic anhydride (P-Y/G@NHs) on non-small cell lung cancer (NSCLC) cell radiosensitivity. Firstly, utilizing the coupling reaction and layer-by-layer assembly technique, P-Y/G@NHs was prepared. The therapeutic effects of the P-Y/G@NHs in NSCLC cells in relation to the PI3K/AKT signaling pathway were examined by assessing the colony formation, apoptosis, and reactive oxygen species (ROS) generation of A549 cells under 10 Gy X-rays irradiation. Moreover, A549 tumor-bearing mice were generated to further validate the therapeutic effect in vivo. We confirmed the successful conjugation of the nanocomposite. Under 10 Gy X-rays irradiation, P-Y/G@NHs reduced the number of colonies of A549 cells, while inducing both cell apoptosis and ROS production. Moreover, P-Y/G@NHs enhanced the radiosensitivity of A549 cells by inhibiting the PI3K/AKT signaling pathway. In vivo fluorescence experiments validated that P-Y/G@NHs effectively-targeted and accumulated at the tumor site in nude mice, thus augmenting the radiosensitivity of tumors without significant immune toxicity or side effects. Conclusively, our findings highlighted that P-Y/G@NHs significantly enhanced the radiosensitivity of NSCLC cells by repressing the PI3K/AKT signaling pathway.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Nanopartículas Metálicas , Animais , Camundongos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Camundongos Nus , Espécies Reativas de Oxigênio/metabolismo , Ouro/farmacologia , Linhagem Celular Tumoral , Transdução de Sinais , Apoptose , Proliferação de Células
12.
Biomater Adv ; 145: 213272, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36586204

RESUMO

A novel hybrid nanocomposite formed of carboxylated Nano Graphene Oxide (c-NGO), highly densely decorated by monodisperse citrate-coated Au nanoparticles (c-NGO/Au NPs), is synthesized and thoroughly characterized for photothermal applications. A systematic investigation of the role played by the synthetic parameters on the Au NPs decoration of the c-NGO platform is performed, comprehensively studying spectroscopic and morphological characteristics of the achieved nanostructures, thus elucidating their still not univocally explained synthesis mechanism. Remarkably, the Au NPs coating density of the c-NGO sheets is much higher than state-of-the-art systems with analogous composition prepared with different approaches, along with a higher NPs size dispersion. A novel theoretical approach for estimating the average number of NPs per sheet, combining DLS and TEM results, is developed. The assessment of the c-NGO/Au NPs photothermal activity is performed under continuous wave (CW) laser irradiation, at 532 nm and 800 nm, before and after functionalization with PEG-SH. c-NGO/Au NPs composite behaves as efficient photothermal agent, with a light into heat conversion ability higher than that of the single components. The c-NGO/Au NPs compatibility for photothermal therapy is assessed by in vitro cell viability tests, which show no significant effects of c-NGO/Au NPs, as neat and PEGylated, on cell metabolic activity under the investigated conditions. These results demonstrate the great potential held by the prepared hybrid nanocomposite for photothermal conversion technologies, indicating it as particularly promising platform for photothermal ablation of cancer cells.


Assuntos
Nanopartículas Metálicas , Óxidos , Óxidos/farmacologia , Óxidos/química , Ouro/farmacologia , Ouro/química , Linhagem Celular Tumoral , Nanopartículas Metálicas/uso terapêutico , Nanopartículas Metálicas/química , Lasers
13.
J Colloid Interface Sci ; 633: 786-799, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36493743

RESUMO

The antimicrobial action of gold depends on different factors including its oxidation state in the intra- and extracellular medium, the redox potential, its ability to produce reactive oxygen species (ROS), the medium components, the properties of the targeted bacteria wall, its penetration in the bacterial cytosol, the cell membrane potential, and its interaction with intracellular components. We demonstrate that different gold species are able to induce bacterial wall damage as a result of their electrostatic interaction with the cell membrane, the promotion of ROS generation, and the consequent DNA damage. In-depth genomic and proteomic studies on Escherichia coli confirmed the superior toxicity of Au (III) vs Au (I) based on the different molecular mechanisms analyzed including oxidative stress, bacterial energetic metabolism, biosynthetic processes, and cell transport. At equivalent bactericidal doses of Au (III) and Au (I) eukaryotic cells were not as affected as bacteria did, maintaining unaffected cell viability, morphology, and focal adhesions; however, increased ROS generation and disruption in the mitochondrial membrane potential were also observed. Herein, we shed light on the antimicrobial mechanisms of ionic and biogenic gold nanoparticles against bacteria. Under selected conditions antibiotic-like ionic gold can exert a strong antimicrobial activity while being harmless to human cells.


Assuntos
Anti-Infecciosos , Nanopartículas Metálicas , Humanos , Antibacterianos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Ouro/farmacologia , Proteômica , Anti-Infecciosos/farmacologia , Bactérias/metabolismo , Escherichia coli/metabolismo , Íons
14.
ACS Nano ; 17(1): 515-529, 2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-36580577

RESUMO

Pyroptosis is gasdermin-mediated programmed necrosis that exhibits promising potential application in cancer immunotherapy, and the main challenge lies in how to provoke specific pyroptosis of tumor cells. Here, biGC@PNA with a precisely stoichiometric ratio of Au(I) ion/Au(0) atom induced pyroptosis of tumor cells by its radiofrequency (RF)-heating effect. An in vitro/in vivo assay on 4T1 tumor cells indicates RF-activated pyroptosis of tumor cells elicits a robust ICD effect, enhancing the synergistic antitumor efficacy of biGC@PNA with decitabine, significantly suppressing tumor metastasis and relapse by provoking systemic antitumor immune responses. Utilizing RF-activated pyroptotic immune responses, biGC@PNA efficiently enhances the antitumor efficacy of αPD-1 immunotherapy under RF irradiation and provides a promising strategy for improving cancer immunotherapy by the noninvasive RF field with high clinical transformation potential.


Assuntos
Neoplasias , Piroptose , Humanos , Ouro/farmacologia , Apoptose , Neoplasias/terapia , Neoplasias/patologia , Imunoterapia
15.
Int J Nanomedicine ; 17: 6095-6112, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36514376

RESUMO

Introduction: Metal nanoparticle synthesis using plant has emerged as an eco-friendly, clean, and viable strategy alternative to chemical and physical approaches. Methods: The fruit extract of Salvadora persica (SP) was utilized as a reducing and stabilizing agent in the synthesis of gold (AuNPs) and copper (CuNPs) nanoparticles. Results: UV-Vis spectra of the AuNPs and CuNPs showed peaks at the wavelengths of 530 nm and 440 nm, respectively. Transmission electron microscopy showed that nanoparticles exhibited a mainly spherical form, with a distribution range of 100 to 113 nm in diameter for AuNPs and of 130 to 135 nm in diameter for CuNPs. While energy-dispersive X-ray spectroscopy was able to confirm the existence of AuNPs and CuNPs. The alcoholic extract of the fruit SP was analyzed by GC-MS in order to identify whether or not it contained any active phytochemicals. Fourier-transform infrared spectra confirmed the presence capping functional biomolecules of SP on the surface of nanoparticles that acts as stabilizers. Analysis of the zeta potential revealed that NPs with high degree of stability, as demonstrated by a strong negative potential value in the range of 25.2 to 28.7 mV. Results showed that both green AuNPs and CuNPs have potential antimicrobial activity against human pathogens such gram-negative bacteria and gram-positive bacteria, with CuNPs having antimicrobial activity higher than AuNPs. In addition, AuNPs and CuNPs have promising antioxidant and anticancer properties when applied to MCF-7 and MDA-MB-231 breast cancer cells. Studies of molecular docking of SP bioactive compounds were conducted against methenyl tetrahydrofolate synthetase. Among all of them, Beta - Sitosterol was the most prominent. Conclusion: These AuNPs and CuNPs are particularly appealing in a variety of applications in the pharmaceutical and medicinal industries due to their economical and environmentally friendly production.


Assuntos
Nanopartículas Metálicas , Salvadoraceae , Humanos , Ouro/farmacologia , Ouro/química , Nanopartículas Metálicas/química , Cobre/farmacologia , Cobre/química , Frutas , Simulação de Acoplamento Molecular , Testes de Sensibilidade Microbiana , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Antibacterianos/química , Química Verde , Espectroscopia de Infravermelho com Transformada de Fourier
16.
Nanomedicine (Lond) ; 17(22): 1663-1676, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36515357

RESUMO

Aim: To investigate the antifungal activity of two different functionalized gold nanoparticles (AuNP), those stabilized with cetyltrimethylammonium bromide and those conjugated with cysteine, and their effects on the architecture of Candida tropicalis biofilms. Materials & methods: Biofilms were studied by crystal violet binding assay and scanning electron microscopy. We investigated the effects of AuNPs on reactive oxygen species, reactive nitrogen intermediates and enzymatic and nonenzymatic antioxidant defenses. Results/Conclusion: The fungicidal activity and cellular stress of both AuNPs affected biofilm growth through accumulation of reactive oxygen species and reactive nitrogen intermediates. However, cetyltrimethylammonium bromide-stabilized AuNPs revealed a higher redox imbalance. We correlated, for the first time, AuNP effects with the redox imbalance and alterations in the architecture of C. tropicalis biofilms.


Biofilms are at least 100­1000-times more resistant to the effects of antimicrobial agents compared with planktonic cells, and nanoparticles have emerged to provide new approaches to improve the safety and efficacy of antimicrobial therapy. The aim of this work was to investigate the antifungal activity with two different functionalized gold nanoparticles. A significant reduction of Candida tropicalis biofilms with alterations in surface topography and architecture was observed, and the oxidative and nitrosative stress affected the biofilms. To the best of our knowledge, this is the first study that attempts to correlate the antibiofilm effects of gold nanoparticles on the redox imbalance against biofilms. These compounds could be an alternative to fungal biofilms infections treatments, applied specifically in biological and medical fields.


Assuntos
Candida tropicalis , Nanopartículas Metálicas , Ouro/farmacologia , Cetrimônio/farmacologia , Antifúngicos/farmacologia , Biofilmes , Testes de Sensibilidade Microbiana
17.
Chem Commun (Camb) ; 59(2): 195-198, 2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36477026

RESUMO

Hierarchical plasmonic nanostructures comprising gold nanorod (AuNR)-covered microballs via syringe-injection reduction show good potential for selective single-cell calcium ionophore (A23187) delivery and apoptosis induction in heterogenous cancer cells.


Assuntos
Nanoestruturas , Nanotubos , Ionóforos de Cálcio , Nanotubos/química , Linhagem Celular Tumoral , Ouro/farmacologia , Ouro/química
18.
An Acad Bras Cienc ; 94(suppl 4): e20211081, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36541976

RESUMO

Cholesterol is a lipid molecule of great biological importance to animal cells. Dysregulation of cholesterol metabolism leads to raised blood total cholesterol levels, a clinical condition called hypercholesterolemia. Evidence has shown that hypercholesterolemia is associated with the development of liver and heart disease. One of the mechanisms underlying heart and liver alterations induced by hypercholesterolemia is oxidative stress. In this regard, in several experimental studies, gold nanoparticles (AuNP) displayed antioxidant properties. We hypothesized that hypercholesterolemia causes redox system imbalance in the liver and cardiac tissues, and AuNP treatment could ameliorate it. Young adult male Swiss mice fed a regular rodent diet or a high cholesterol diet for eight weeks and concomitantly treated with AuNP (2.5 µg/kg) or vehicle by oral gavage. Hypercholesterolemia increased the nitrite concentration and glutathione (GSH) levels and decreased the liver's superoxide dismutase (SOD) activity. Also, hypercholesterolemia significantly enhanced the reactive oxygen species (ROS) and GSH levels in cardiac tissue. Notably, AuNP promoted the redox system homeostasis, increasing the SOD activity in hepatic tissue and reducing ROS levels in cardiac tissue. Overall, our data showed that hypercholesterolemia triggered oxidative stress in mice's liver and heart, which was partially prevented by AuNP treatment.


Assuntos
Hipercolesterolemia , Nanopartículas Metálicas , Camundongos , Animais , Masculino , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/etiologia , Ouro/metabolismo , Ouro/farmacologia , Ouro/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Antioxidantes/metabolismo , Colesterol , Estresse Oxidativo , Dieta , Fígado , Glutationa , Superóxido Dismutase/metabolismo
19.
Int J Mol Sci ; 23(24)2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36555417

RESUMO

Photodynamic therapy (PDT) is currently regarded as a promising method for the treatment of oncological diseases. However, it involves a number of limitations related to the specific features of the method and the specific characteristics of photosensitizer molecules, including tumor hypoxia, small depth of light penetration into the tumor tissue, and low accumulation sensitivity. These drawbacks can be overcome by combining PDT with other treatment methods, for example, chemotherapy. In this work, we were the first to obtain agents that contain bacteriopurpurinimide as a photodynamic subunit and complexes of gold(I) that implement the chemotherapy effect. To bind the latter agents, N-heterocyclic carbenes (NHC) based on histidine and histamine were obtained. We considered alternative techniques for synthesizing the target conjugates and selected an optimal one that enabled the production of preparative amounts for biological assays. In vitro studies showed that all the compounds obtained exhibited high photoinduced activity. The C-donor Au(I) complexes exhibited the maximum specific activity at longer incubation times compared to the other derivatives, both under exposure to light and without irradiation. In in vivo studies, the presence of histamine in the NHC-derivative of dipropoxy-BPI (7b) had no significant effect on its antitumor action, whereas the Au(I) metal complex of histamine NHC-derivative with BPI (8b) resulted in enhanced antitumor activity and in an increased number of remissions after photodynamic treatment.


Assuntos
Complexos de Coordenação , Neoplasias , Fotoquimioterapia , Humanos , Complexos de Coordenação/farmacologia , Histidina , Histamina , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias/tratamento farmacológico , Ouro/farmacologia , Linhagem Celular Tumoral
20.
Molecules ; 27(24)2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36557818

RESUMO

Antimicrobial resistance has posed a serious health concern worldwide, which is mainly due to the excessive use of antibiotics. In this study, gold nanoparticles synthesized from the plant Tinospora cordifolia were used against multidrug-resistant Pseudomonas aeruginosa. The active components involved in the reduction and stabilization of gold nanoparticles were revealed by gas chromatography-mass spectrophotometry(GC-MS) of the stem extract of Tinospora cordifolia. Gold nanoparticles (TG-AuNPs) were effective against P. aeruginosa at different concentrations (50,100, and 150 µg/mL). TG-AuNPs effectively reduced the pyocyanin level by 63.1% in PAO1 and by 68.7% in clinical isolates at 150 µg/mL; similarly, swarming and swimming motilities decreased by 53.1% and 53.8% for PAO1 and 66.6% and 52.8% in clinical isolates, respectively. Biofilm production was also reduced, and at a maximum concentration of 150 µg/mL of TG-AuNPs a 59.09% reduction inPAO1 and 64.7% reduction in clinical isolates were observed. Lower concentrations of TG-AuNPs (100 and 50 µg/mL) also reduced the pyocyanin, biofilm, swarming, and swimming. Phenotypically, the downregulation of exopolysaccharide secretion from P. aeruginosa due to TG-AuNPs was observed on Congo red agar plates.


Assuntos
Nanopartículas Metálicas , Pseudomonas aeruginosa , Ouro/farmacologia , Piocianina/farmacologia , Biofilmes , Antibacterianos/farmacologia
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