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1.
Sci Total Environ ; 954: 176847, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39393706

RESUMO

The degradation of high-density polyethylene (HDPE) in marine environments was investigated under various weathering conditions. HDPE debris were collected from coastal areas near Korinthos, Greece which had been exposed to marine conditions for durations ranging from a few months to several decades; they were analysed alongside with laboratory-manufactured HDPE specimens subjected to controlled weathering exposure. Four (4) different cases were investigated, including exposure to different conditions, namely to (a) natural atmospheric and (b) sea weathering conditions, (c) accelerated ultraviolet (UV) radiation, and finally (d) submersion to artificial seawater for up to twelve (12) months. The degradation assessment was proposed based on performed tensile mechanical tests, while the chemical/microstructural changes were assessed through Fourier Transform Infrared (FTIR) spectroscopy and Scanning Electron Microscopy (SEM). FTIR spectroscopy indicated the emergence of carbonyl groups, with peaks appearing between 1740 cm-1 and 1645 cm-1, which are crucial indicators of photo-oxidative degradation. Key findings revealed that HDPE specimens experienced significant (8 %) ultimate tensile strength (σUTS) only after 3 months of atmospheric exposure, while this decrease can reach up to 60 % over the period of 35 years exposure. A strong correlation was observed between the σUTS decrease between the (a) natural environment and (b) accelerated UV weathering exposure. It is noticed that 1½ month of accelerated UV exposure corresponded to similar ultimate tensile strength decrease for 6 months of natural atmospheric degradation. A linear correlation is proposed to assess the long-term materials' tensile properties degradation in marine environments.

2.
Heliyon ; 10(17): e35634, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39295985

RESUMO

Optical and photocatalytic restrictions of anatase TiO2 nanoparticles (Nps) limit their potential applications, as antipollutant and antibacterial agents for sanitary applications, to the UV spectral region. While modification with transition metals extends the absorption capacity to the visible light spectrum, often undermines the photocatalysts' biocompatibility due to toxic ion leaching. In this study, we synthesized Cu-doped and Ag-decorated TiO2 photocatalysts by employing solvothermal (ATiO2:Cu) and sol-gel synthetic procedures (BTiO2:Ag), respectively. We acquired TiO2 Nps modified with three percentages of either Cu or Ag content, to examine the potential differentiation of their structural, photocatalytic, and biological impact. Comprehensive structural characterization supports the prevailing anatase crystalline structure of bare and modified titania nanostructures, while morphological differences are demonstrated among the different samples. Optical response in the visible region of ATiO2:Cu Nps stems from band gap narrowing and lattice-defect generation, while plasmonic effects are at play for BTiO2:Ag Nps. Their photocatalytic potential under visible light irradiation, originated from low-energy LED lamps commonly found in indoor spaces, was verified after monitoring the successful enhancement of methylene blue (MB) degradation rate. Safety assessment on immortalized healthy human keratinocyte cell line (HaCaT) revealed their biocompatibility up to a certain concentration, while reactive oxygen species (ROS) production was intensified after light irradiation. The visible-light-induced photocatalytic-driven antibacterial activity was confirmed against both gram-positive Staphylococcus aureus and gram-negative Escherichia coli.

3.
Pharmaceutics ; 16(4)2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38675188

RESUMO

This study investigates the distinctive characteristics of iron oxide magnetic nanoparticles (mNPs) and their potential application in cancer therapy, focusing on melanoma. Three types of mNPs, pre-validated for safety, underwent molecular analysis to uncover the activated signaling pathways in melanoma cells. Using the Western blot technique, the study revealed that mNPs induce cytotoxicity, hinder proliferation through ERK1/2 dephosphorylation, and prompt proapoptotic effects, including DNA damage by inducing H2AX phosphorylation. Additionally, in vitro magnetic hyperthermia notably enhanced cellular damage in melanoma cells. Moreover, the quantification of intracellular iron levels through Inductively Coupled Plasma Mass Spectrometry (ICP-MS) analysis unveils the precise dosage required to induce cellular damage effectively. These compelling findings not only shed light on the therapeutic potential of mNPs in melanoma treatment but also open exciting avenues for future research, heralding a new era in the development of targeted and effective cancer therapies. Indeed, by discerning the effective dose, our approach becomes instrumental in optimizing the therapeutic utilization of iron oxide magnetic nanoparticles, enabling the induction of precisely targeted and controlled cellular responses.

4.
Transl Oncol ; 45: 101961, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38631259

RESUMO

Tumor microenvironment is an intricate web of stromal and immune cells creating an immune suppressive cordon around the tumor. In hepatocellular carcinoma (HCC), Tumor microenvironment is a formidable barrier towards novel immune therapeutic approaches recently evading the oncology field. In this study, the main aim was to identify the intricate immune evasion tactics mediated by HCC cells and to study the epigenetic modulation of the immune checkpoints; Programmed death-1 (PD-1)/ Programmed death-Ligand 1 (PD-L1) and T cell immunoreceptor with Ig and ITIM domains (TIGIT)/Cluster of Differentiation 155 (CD155) at the tumor-immune synapse. Thus, liver tissues, PBMCs and sera were collected from Hepatitis C Virus (HCV), HCC as well as healthy individuals. Screening was performed to PD-L1/PD-1 and CD155/TIGIT axes in HCC patients. PDL1, CD155, PD-1 and TIGIT were found to be significantly upregulated in liver tissues and peripheral blood mononuclear cells (PBMCs) of HCC patients. An array of long non-coding RNAs (lncRNAs) and microRNAs validated to regulate such immune checkpoints were screened. The lncRNAs; CCAT-1, H19, and MALAT-1 were all significantly upregulated in the sera, PBMCs, and tissues of HCC patients as compared to HCV patients and healthy controls. However, miR-944-5p, miR-105-5p, miR-486-5p, miR-506-5p, and miR-30a-5p were downregulated in the sera and liver tissues of HCC patients. On the tumor cell side, knocking down of lncRNAs-CCAT-1, MALAT-1, or H19-markedly repressed the co-expression of PD-L1 and CD155 and accordingly induced the cytotoxicity of co-cultured primary immune cells. On the immune side, ectopic expression of the under-expressed microRNAs; miR-486-5p, miR-506-5p, and miR-30a-5p significantly decreased the transcript levels of PD-1 in PBMCs with no effect on TIGIT. On the other hand, ectopic expression of miR-944-5p and miR-105-5p in PBMCs dramatically reduced the co-expression of PD-1 and TIGIT. Finally, all studied miRNAs enhanced the cytotoxic effects of PBMCs against Huh7 cells. However, miR-105-5p showed the highest augmentation for PBMCs cytotoxicity against HCC cells. In conclusion, this study highlights a novel co-targeting strategy using miR-105-5p mimics, MALAT-1, CCAT-1 and H19 siRNAs to efficiently hampers the immune checkpoints; PD-L1/PD-1 and CD155/TIGIT immune evasion properties in HCC.

5.
ACS Omega ; 8(47): 44424-44436, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38046305

RESUMO

To provide precise medical regimens, photonics technologies have been involved in the field of nanomedicine. Phototriggered liposomes have been cast as promising nanosystems that achieve controlled release of payloads in several pathological conditions such as cancer, autoimmune, and infectious diseases. In contrast to the conventional liposomes, this photoresponsive element greatly improves therapeutic efficacy and reduces the adverse effects of gene/drug therapy during treatment. Recently, cancer immunotherpay has been one of the hot topics in the field of oncology due to the great success and therapeutic benefits that were well-recognized by the patients. However, several side effects have been encountered due to the unmonitored augmentation of the immune system. This Review highlights the most recent advancements in the development of photoresponsive liposome nanosystems in the field of oncology, with a specific emphasis on challenges and opportunities in the field of cancer immunotherapy.

6.
ACS Appl Bio Mater ; 6(12): 5235-5251, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-37955979

RESUMO

Cancer is one of the leading causes of death worldwide. Conventional therapies lack selectivity and suffer from toxicity and drug resistance, leading to metastasis. To overcome these limitations, a new category of nanomaterials exploiting the tumor characteristics has been developed in cancer nanotherapeutics. Among them, pH, metabolism, and the disrupted architecture of cells can be exploited for theranostic applications. Such nanomaterials can be inorganic nanoparticles with silver ones and gain high attention as diagnostic, therapeutic, and antibacterial compounds. Silver has been linked with triggering the death of cancer cells via DNA damage due to the production of reactive oxygen species (ROS) during photodynamic therapy. Thus, improvement of biocompatibility, modification with targeted agents, and drug conjugation promote the use of silver nanoparticles. In this work, we managed to synthesize hybrid Ag@SiO2 core-shell nanoparticles via a modified sol-gel method by tackling the known etching of silver caused by ammonia by employing different bases of the sol-gel reaction. The bases used in the synthetic route were diethylamine (DEA) and triethylamine (TEA) and were monitored with silver nanoparticles individually from the absorbance peak of silver in the UV-vis region, showing no etching of silver in contrast with ammonia, which is usually used in the sol-gel method. Furthermore, we synthesized biocompatible nanoparticles with anticancer and diagnostic properties toward breast cancer cells and glioblastoma cells. The nanoparticles were characterized both structurally and morphologically. Their biological evaluation suggests minor toxicity toward healthy cells and red blood cells (RBCs). Also, the diagnostic potential of the hybrid nanoparticles was exploited by optical fluorescence microscopy. Therefore, we strongly suggest the investigation of such nanostructures as a dual platform for the diagnosis and therapy of cancer.


Assuntos
Nanopartículas Metálicas , Neoplasias , Humanos , Prata/química , Nanopartículas Metálicas/uso terapêutico , Nanopartículas Metálicas/química , Dióxido de Silício/química , Medicina de Precisão , Amônia
7.
Nanoscale Adv ; 5(19): 5399-5413, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37767043

RESUMO

Herein, thermo-responsive liposomes (TLs) loaded with Asp (Asp/TLs) were produced by self-assembling DPPC, DSPE-PEG2000, and cholesterol. The preparation variables were optimized using the Box-Behnken design (BBD). The optimized Asp/TLs exhibited an average particle size of 114.05 ± 1.56 nm, PDI of 0.15 ± 0.015, zeta potential of -15.24 ± 0.65 mV, and entrapment efficiency (EE%) of 84.08 ± 2.75%. In addition, under physiological conditions, Asp/TLs showed spherical shape, outstanding stability and thermo-triggered the release of Asp at 38 °C, reaching the maximum Asp release at 40 °C. The MTT assay showed that the optimal Asp/TLs exhibited the highest cytotoxic activity upon exposure to mild hyperthermia (40 °C) against the invasive triple-negative breast cancer cell line (MDA-MB-231) when compared to other preparations. The IC50 of Asp/TLs (40 °C) was estimated at 0.9 µg mL-1, while that of free Asp (40 °C) was 3.83 µg mL-1. As such, the optimal Asp/TLs were shown to increase the cytotoxic activity of Asp by 4-fold upon exposure to mild hyperthermia. The IC50 values of Asp and Asp/TLs without exposure to 40 °C were 6.6 µg mL-1 and 186 µg mL-1, respectively. This indicated that Asp was released only when placed at 40 °C. The apoptosis assay revealed that Asp/TLs (40 °C) caused a remarkable increase in the percentage of cell population among both the late apoptosis and necrosis quartiles, as well as a significant decline in the viable cell quartile (P ≤ 0.001) when compared to Asp (40 °C). Asp/TLs (40 °C) and Asp (40 °C) could stimulate the intrinsic apoptosis pathway by upregulating the apoptotic genes Bak and Bax, while downregulating the anti-apoptotic genes, BCL-xL and BCL-2. The free Asp (40 °C) increased the gene expression of Bak and Bax by 4.4- and 5.2-folds, while reducing the expression of BCL-xL and BCL-2 by 50% and 73%, respectively. The optimal Asp TLs (40 °C) manifested more potent effects as demonstrated by the upregulation of Bak, Bax, and P53 by 5.6-, 7.2-, and 1.3-folds, as well as the downregulation of BCL-xL and BCL-2 by 70% and 85%, respectively. As such, the optimal Asp TLs (40 °C) treatment displayed the most potent cytotoxic profile and induced both apoptosis and necrosis in MDA-MB-231.

8.
Front Nucl Med ; 3: 1184309, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-39380961

RESUMO

Introduction: Prostate cancer (PCa) is the second most frequent cancer diagnosis in men and the fifth leading cause of death worldwide. Prostate Specific Membrane Antigen (PSMA) and Gastrin Releasing Peptide (GRP) receptors are overexpressed in PCa. In this study, we have developed iron oxide nanoparticles (IONs) functionalized with the Prostate Specific Membrane Antigen (PSMA) and Gastrin Releasing Peptide (GRP) ligands for dual targeting of Prostate cancer. Methods: IONs were developed with a thin silica layer on their surface with MPTES (carrying -SH groups, IONs-SH), and they were coupled either with a pharmacophore targeting PSMA (IONs-PSMA) or with bombesin peptide (IONs-BN), targeting GRP receptors, or with both (IONs-PSMA/BN). The functionalized IONs were characterized for their size, zeta potential, and efficiency of functionalization using dynamic light scattering (DLS) and Fourier-Transform Infrared Spectroscopy (FT-IR). All the aforementioned types of IONs were radiolabeled directly with Technetium-99m (99mTc) and evaluated for their radiolabeling efficiency, stability, and binding ability on two different PCa cell lines (PC3 and LNCaP). Results and Discussion: The MTT assay demonstrated low toxicity of the IONs against PC3 and LNCaP cells, while the performed wound-healing assay further proved that these nanostructures did not affect cellular growth mechanisms. The observed hemolysis ratio after co-incubation with red blood cells was extremely low. Furthermore, the 99mTc-radiolabeled IONs showed good stability in human serum, DTPA, and histidine, and high specific binding rates in cancer cells, supporting their future utilization as potential diagnostic tools for PCa with Single Photon Emission Computed Tomography (SPECT) imaging.

9.
Biomolecules ; 12(8)2022 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-36008969

RESUMO

The consequences of aging and disease conditions in tissues involve reactive oxygen species (ROS) and related molecular alterations of different cellular compartments. We compared a murine model of immunodeficient (SCID) xenografted young (4 weeks old) and old (17 weeks old) mice with corresponding controls without tumor implantation and carried out a compositional evaluation of brain tissue for changes in parallel DNA and lipids compartments. DNA damage was measured by four purine 5',8-cyclo-2'-deoxynucleosides, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG), and 8-oxo-7,8-dihydro-2'-deoxyadenosine (8-oxo-dA). In brain lipids, the twelve most representative fatty acid levels, which were mostly obtained from the transformation of glycerophospholipids, were followed up during the aging and disease progressions. The progressive DNA damage due to age and tumoral conditions was confirmed by raised levels of 5'S-cdG and 5'S-cdA. In the brain, the remodeling involved a diminution of palmitic acid accompanied by an increase in arachidonic acid, along both age and tumor progressions, causing increases in the unsaturation index, the peroxidation index, and total TFA as indicators of increased oxidative and free radical reactivity. Our results contribute to the ongoing debate on the central role of DNA and genome instability in the aging process, and on the need for a holistic vision, which implies choosing the best biomarkers for such monitoring. Furthermore, our data highlight brain tissue for its lipid remodeling response and inflammatory signaling, which seem to prevail over the effects of DNA damage.


Assuntos
Ácidos Graxos , Neoplasias , 8-Hidroxi-2'-Desoxiguanosina , Envelhecimento , Animais , Encéfalo , DNA , Dano ao DNA , Camundongos , Camundongos SCID , Neoplasias/genética , Purinas
10.
Colloids Surf B Biointerfaces ; 214: 112463, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35316703

RESUMO

A drug delivery nanosystem of noble bimetallic nanoparticles (NPs) which consists of Au NPs capped with Pt NPs (Au@Pt NPs) is constructed and functionalised with a quinazoline based small molecule (Au@Pt@Q NPs), acting as a theranostic agent against glioblastoma. Two different hydrothermal synthetic procedures for bimetallic Au@Pt NPs are presented and the resulting nanostructures are fully characterised by means of spectroscopic and microscopic methods. The imaging and targeting capacity of the new drug delivery system is assessed through fluorescent optical microscopy and cytotoxicity evaluations. The constructed Au@Pt NPs consist a monodispersed colloidal solution of 25 nm with photoluminescent, fluorescent and X-Ray absorption properties that confirm their diagnostic potential. Haemolysis testing demonstrated that Au@Pt NPs are biocompatible and fluorescent microscopy confirmed their entering the cells. Cytological evaluation of the NPs through MTT assay showed that they do not inhibit the proliferation of control cell line HEK293, whereas they are toxic in U87MG, U251 and D54 glioblastoma cell lines; rendering them selective targeting agents for treating glioblastoma.


Assuntos
Glioblastoma , Nanopartículas Metálicas , Sistemas de Liberação de Medicamentos , Glioblastoma/tratamento farmacológico , Ouro/química , Células HEK293 , Humanos , Nanopartículas Metálicas/química , Platina/química
11.
Dalton Trans ; 51(9): 3452-3461, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35037008

RESUMO

Semiconducting nanoparticles called quantum dots (Qds) present unique optoelectronic properties based on their extremely small size, composition, and spherical shape, which make them suitable for use as diagnostic and theranostic agents in biological samples. The main scope of the fabrication of Qds is real-time diagnosis, therapy, drug delivery, and in vitro and in vivo tracking, presenting strong resistance to photobleaching. In this work, quantum dots such as ZnO, ZnSe, ZnS, and doped ZnS : Mn and ZnS : Cd were developed via a simple sol-gel synthesis in an aqueous solution. Morphological, structural, and optical characterizations were investigated. Moreover, an in vitro biological evaluation of Qds was performed. The results indicate that the photoluminescence is enhanced after doping ZnS Qds with Mn2+ and Cd2+. Qds have been synthesized for use as fluorescent agents for real-time monitoring in bio-applications.


Assuntos
Pontos Quânticos
12.
Bioinorg Chem Appl ; 2021: 5599773, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093697

RESUMO

Herein, we report the synthesis and characterization of a bishomoleptic and a trisheteroleptic ruthenium (II) polypyridyl complex, namely, [Ru(bpy)2(2, 2'-pq)](PF6)2 (1) and [Ru(bpy) (phen) (2, 2'-pq)](PF6)2 (2), respectively, where bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline, and 2, 2'-pq = 2-(2'-pyridyl)-quinoxaline. The complexes were characterized by elemental analysis, TGA, 1H-NMR, FT-IR, UV-Vis, emission spectroscopy, and electrochemistry. Their structures were confirmed by single-crystal X-ray diffraction analysis. Complexes 1 and 2 were crystalized in orthorhombic, Pbca, and monoclinic, P21/n systems, respectively. Various spectroscopic techniques were employed to investigate the interaction of both complexes with calf thymus DNA (CT-DNA). The experimental data were confirmed by molecular docking studies, employing two different DNA sequences. Both complexes, 1 and 2, bind with DNA via a minor groove mode of binding. MTT experiments revealed that both complexes induce apoptosis of MCF-7 (breast cancer) cells in low concentrations. Confocal microscopy indicated that 2 localizes in the nucleus and internalizes more efficiently in MCF-7 than in HEK-293.

13.
Materials (Basel) ; 14(4)2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33546176

RESUMO

The scientific community has made great efforts in advancing magnetic hyperthermia for the last two decades after going through a sizeable research lapse from its establishment. All the progress made in various topics ranging from nanoparticle synthesis to biocompatibilization and in vivo testing have been seeking to push the forefront towards some new clinical trials. As many, they did not go at the expected pace. Today, fruitful international cooperation and the wisdom gain after a careful analysis of the lessons learned from seminal clinical trials allow us to have a future with better guarantees for a more definitive takeoff of this genuine nanotherapy against cancer. Deliberately giving prominence to a number of critical aspects, this opinion review offers a blend of state-of-the-art hints and glimpses into the future of the therapy, considering the expected evolution of science and technology behind magnetic hyperthermia.

14.
Methods Mol Biol ; 2207: 85-97, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33113129

RESUMO

This chapter focuses on the in vitro biological evaluation of multisensitive nanocontainers as drug delivery systems for cancer treatment. Cancer tissues possess some unique characteristics such as increased temperature due to inflammation, thermal vulnerability (40-45 °C), low cellular pH, and redox instabilities. The employment of polymers bearing pH, thermo, and/or redox sensitivities in the synthesis of hollow polymeric nanostructures has led to the formulation of a variety of drug delivery vehicles that are capable of targeted delivery and trigger specific drug release. The cavity in the structure allows for the encapsulation of anticancer drugs as well as other moieties with anticancer activity, like iron oxide magnetic nanoparticles. The drug loading and release capability of the nanocontainers is evaluated prior to biological studies in order to determine the concentration of the drug in the structure. The in vitro assessment includes cytotoxicity studies, quantitatively through the colorimetric MTT assay as well as qualitatively via the scratch-wound healing assay, on both cancer and healthy cell lines. The cellular localization of the studied drug-loaded and unloaded nanocontainers is determined through confocal fluorescence microscopy.


Assuntos
Antineoplásicos , Portadores de Fármacos , Nanopartículas de Magnetita , Neoplasias , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Avaliação Pré-Clínica de Medicamentos , Humanos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia
15.
Methods Mol Biol ; 2207: 151-161, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33113134

RESUMO

Common chemotherapeutic drugs exhibit no specificity for cancer cells and destroy simultaneously healthy cells exhibiting high toxicity and reduced efficacy. The use of nanotechnology, especially of drug delivery systems to the size of the nanoscale, provides rational drug design solutions. Such nanomaterials may have a range of desired characteristics (lack of toxicity, response to certain characteristics of the cancer cells, antimicrobial properties, specific activity, etc.) in order to achieve targeted cancer therapy. In this chapter, polymeric systems with core-shell structure are synthesized, characterized, and studied as potent drug delivery devices for targeted cancer therapy. These polymeric systems are based on natural polysaccharides like cellulose, chitosan, and their derivatives, in combination with synthetic polymer. Polymethylmethacrylate (PMMA) nanospheres are used as a core in order to coat the surface with multiple layers of polysaccharides via layer-by-layer deposition. This design is advantageous due to the use of water as the appropriate solvent. Fabricated polymeric carriers are characterized structurally by AT-IR spectroscopy and morphologically by transmission (TEM) and scanning electron microscopy (SEM). Finally, daunorubicin, an anticancer agent, was encapsulated as a drug model into the carriers.


Assuntos
Antineoplásicos , Celulose/química , Quitosana/química , Portadores de Fármacos , Nanosferas , Neoplasias/tratamento farmacológico , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Humanos , Nanosferas/química , Nanosferas/uso terapêutico , Neoplasias/metabolismo , Neoplasias/patologia , Polimetil Metacrilato/química
16.
Chem Res Toxicol ; 33(10): 2565-2572, 2020 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-32865980

RESUMO

Bleomycin has a long-studied mechanism of action through the formation of a complex with metals, such as iron. The bleomycin-iron complex was recently shown to induce membrane damage by free radical reactivity. Because the use of Fe nanoparticles is spreading for drug delivery strategies, molecular mechanisms of cell damage must include different compartments in order to observe the progression of the cell reactivity. In this study, human embryonic kidney (HEK-293) cells were exposed for 24 h to bleomycin and polymeric iron oxide nanoparticles (Fe-NPs), alone or in combination. The fatty acid-based membrane lipidomic analysis evidenced the fatty acid remodeling in response to the treatments. Bleomycin alone caused the increase of saturated fatty acid (SFA) moieties in cell membrane glycerophospholipids with concomitant diminution of monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acid levels. Under Fe-NPs treatment, omega-6 PUFA decreased and trans fatty acid isomers increased. Under coadministration bleomycin and Fe-NPs, all membrane remodeling changes disappeared compared to those of the controls, with only an increase of omega-6 PUFA that elevates peroxidation index remaining. Our results highlight the important role of fatty-acid-based membrane lipidome monitoring to follow up the fatty acid reorganization induced by the drug, to be considered as a side effect of the pharmacological activity, suggesting the need of an integrated approach for the investigation of drug and carrier molecular mechanisms.


Assuntos
Bleomicina/farmacologia , Ácidos Graxos/metabolismo , Compostos Férricos/farmacologia , Glicerofosfolipídeos/metabolismo , Nanopartículas/química , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Células Cultivadas , Células HEK293 , Humanos
17.
J Inorg Biochem ; 211: 111177, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32795713

RESUMO

Recently, there has been ongoing research in the field of nanotechnology and nanomedicine aiming at developing multifunctional biomaterials using noble metals. The unique properties of silver (Ag) are known from ancient times and thus are being explored for their behavior on the nano scale. Silver shows high antimicrobial activity against different microorganisms, while modification of the surface of its nanostructures can be useful in active targeting regarding cancer treatment. During the synthetic procedure, in order to obtain a more uniform sample of silver nanoparticles (Ag NPs) with spherical morphology, a stabilizer is essential. The stabilizers used not only control the progression of the reaction, but also increases the biocompatibility of the NPs. Thus, we managed to synthesize spherical and rod-like Ag NPs via a polyol method and stabilize them with polyvinylpyrrolidone (PVP). The resulted Ag NPs were characterized morphologically with Transmission Electron Microscopy (TEM) and further confirmed by their structural characterization (FT-IR, UV-Vis, Dynamic Light Scattering (DLS) and Zeta Potential). For their biocompatibility profile, we studied their interaction with red blood cells (RBCs) through hemolysis assay and we monitored their structural alterations through SEM. The antimicrobial activity was tested with the agar diffusion disc assay for Gram negative and Gram positive microorganisms E. coli and S. aureus respectively. Nanoparticles' (NPs) internalization and localization studies in cancer cells were monitored with fluorescence microscopy in MCF-7 and U87-MG. According to our results it is worth it to investigate the potential of these nanomaterials since they can have a significant role in applications of theranostics in nanomedicine.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Eritrócitos/efeitos dos fármacos , Nanopartículas Metálicas/administração & dosagem , Neoplasias/tratamento farmacológico , Polímeros/química , Prata/química , Antibacterianos/química , Antineoplásicos/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Escherichia coli/efeitos dos fármacos , Humanos , Nanopartículas Metálicas/química , Nanotecnologia/métodos , Neoplasias/patologia , Medicina de Precisão , Staphylococcus aureus/efeitos dos fármacos , Células Tumorais Cultivadas
18.
J Inorg Biochem ; 208: 111077, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32247891

RESUMO

Two novel copper (II) complexes, namely [Cu(2,2'-pq)(NO3)](NO3) (1) and [Cu(2,2'-pq)2(NO3)](NO3)·6H2O(2) where 2,2'-pq is 2-(2'-pyridyl quinoxaline) were synthesized and characterized by various spectral methods. Complex 2 characterized by single crystal X-ray diffraction showed a distorted trigonal bipyramidal geometry and crystallized together with an hexamer, (H2O)6 cluster, with R66(12) topology and chair conformation. The interaction of Calf Thymus DNA (CT-DNA) with 1 and 2 was investigated by UV-Visible absorption spectra, Viscosity, Cyclic Voltammetry, Fluorescence and Circular Dichroism (CD), indicating that both complexes can bind to DNA both by means of intercalation and groove binding. Their DNA interaction mode depends on their concentrations and the differences between their structures. Cleavage experiments were performed by agarose gel electrophoresis using pBR322 DNA both in dark and after illumination. Furthermore, the cytotoxicity of both complexes was evaluated against MCF-7 and healthy cells (HEK-293) by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays; moreover their cell uptake against MCF-7 tumor cells and HEK-293 normal cells was revealed by using confocal laser scanning. Both complexes have the potential to act as effective anticancer drugs with 2 to present an IC50 smaller than that of cis-platin and also to be useful for optically probing tumor cells since it fluoresces at blue and green when is treated with MCF-7 cells.


Assuntos
Complexos de Coordenação , Cobre , Citotoxinas , DNA/química , Quinoxalinas , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Cobre/química , Cobre/farmacologia , Citotoxinas/síntese química , Citotoxinas/química , Citotoxinas/farmacologia , Células HEK293 , Humanos , Células MCF-7 , Quinoxalinas/síntese química , Quinoxalinas/química , Quinoxalinas/farmacologia
19.
Phys Med ; 71: 39-52, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32088564

RESUMO

PURPOSE: The purpose of this study is to employ magnetic fluid hyperthermia simulations in the precise computation of Specific Absorption Rate functions -SAR(T)-, and in the evaluation of the predictive capacity of different SAR calculation methods. METHODS: Magnetic fluid hyperthermia experiments were carried out using magnetite-based nanofluids. The respective SAR values were estimated through four different calculation methods including the initial slope method, the Box-Lucas method, the corrected slope method and the incremental analysis method (INCAM). A novel numerical model combining the heat transfer equations and the Navier-Stokes equations was developed to reproduce the experimental heating process. To address variations in heating efficiency with temperature, the expression of the power dissipation as a Gaussian function of temperature was introduced and the Levenberg-Marquardt optimization algorithm was employed to compute the function parameters and determine the function's effective branch within each measurement's temperature range. The power dissipation function was then reduced to the respective SAR function. RESULTS: The INCAM exhibited the lowest relative errors ranging between 0.62 and 15.03% with respect to the simulations. SAR(T) functions exhibited significant variations, up to 45%, within the MFH-relevant temperature range. CONCLUSIONS: The examined calculation methods are not suitable to accurately quantify the heating efficiency of a magnetic fluid. Numerical models can be exploited to effectively compute SAR(T) and contribute to the development of robust hyperthermia treatment planning applications.


Assuntos
Hipertermia Induzida/métodos , Magnetismo , Algoritmos , Calorimetria , Simulação por Computador , Temperatura Alta , Humanos , Modelos Lineares , Nanopartículas de Magnetita , Distribuição Normal , Reprodutibilidade dos Testes
20.
J Colloid Interface Sci ; 564: 371-380, 2020 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-31918204

RESUMO

Nanobubbles (ΝΒs) have attracted concentrated scientific attention due to their unique physicochemical properties and large number of potential applications. In this study, a novel nanobubble generator with low energy demand, operating continuously, is presented. Air and oxygen bulk nanobubbles (NBs@air and NBs@O2) with narrow size distribution and outstanding stability were prepared in water solution. The bulk NBs' behavior was evaluated taking into consideration the hydrodynamic diameter and ζ-potential as a function of processing time, gas type, pH value and NaCl concentration. According to the results the optimum processing time was 30 min, whereas the effect of water salinity was stronger in NBs@O2 than NBs@air. In order to investigate further the NBs properties, Electron Paramagnetic Resonance (EPR) spectroscopy was applied for quantitative analysis of free radicals following the spin trapping methodology. The mechanism of bulk NBs' generation and their extremely long-time stability can be attributed mainly to the hydrogen bonding interactions. The formation of a diffusion layer, by absorption of OH- due to electrostatic interaction, contributing to negative surface charge, whereas the interaction of ions with the surface hydroxylic groups provide the equilibrium between the protonation and deprotonation of water and finally the formation of a stable interface layer. A remarkable highlight of this work is the long-time stability of generated bulk NBs which is up to three months.

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