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Polydopamine (PDA) stands as a versatile material explored in cancer nanomedicine for its unique properties, offering opportunities for multifunctional drug delivery platforms. This study explores the potential of utilizing a one-pot synthesis to concurrently integrate Fe, Gd and Mn ions into porous PDA-based theranostic drug delivery platforms called Ferritis, Gadolinis and Manganis, respectively. Our investigation spans the morphology, magnetic properties, photothermal characteristics and cytotoxicity profiles of those potent nanoformulations. The obtained structures showcase a spherical morphology, robust magnetic response and promising photothermal behaviour. All of the presented nanoparticles (NPs) display pronounced paramagnetism, revealing contrasting potential for MRI imaging. Relaxivity values, a key determinant of contrast efficacy, demonstrated competitive or superior performance compared to established, used contrasting agents. These nanoformulations also exhibited robust photothermal properties under near infra-red irradiation, showcasing their possible application for photothermal therapy of cancer. Our findings provide insights into the potential of metal-doped PDA NPs for cancer theranostics.
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Indóis , Imageamento por Ressonância Magnética , Polímeros , Indóis/química , Humanos , Polímeros/química , Meios de Contraste/química , Nanopartículas/química , Nanopartículas/uso terapêutico , Manganês/química , Nanomedicina Teranóstica/métodosRESUMO
Cancer remains a leading cause of mortality worldwide, necessitating the development of innovative therapeutic approaches. Nanoparticle-based drug delivery systems have garnered significant interest due to their multifunctionality, offering the potential to enhance cancer treatment efficacy and improve patient tolerability. Membrane-coated drug delivery systems hold great potential for enhancing the therapeutic outcome of nanoparticle-based anticancer therapies. In this study, we report the synthesis of multifunctional iron-functionalized mesoporous polydopamine nanoparticles (MPDAFe NPs). These nanoformulations demonstrate substantial potential for combining efficient drug delivery and magnetic resonance imaging (MRI) and showcase the advantages of biomimetic coating with tumor cell-derived membranes. This coating confers prolonged circulation and improved the targeting capabilities of the nanoparticles. Furthermore, comprehensive biosafety evaluations reveal negligible toxicity to normal cells, while the combined chemo- and phototherapy exhibited significant cytotoxicity towards cancer cells. Additionally, the photothermal effect evaluation highlights the enhanced cytotoxicity achieved through laser irradiation, showcasing the synergistic effects of the nanomaterials and photothermal therapy. Importantly, our chemotherapeutic effect evaluation demonstrates the superior efficacy of doxorubicin-loaded MPDAFe@Mem NPs (cancer cell membrane-coated MPDAFe NPs) in inhibiting cancer cell viability and proliferation, surpassing the potency of free doxorubicin. This study comprehensively investigates theranostic, membrane-coated drug delivery systems, underlining their potential to increase the efficacy of cancer treatment strategies. The multifunctional nature of the iron-functionalized polydopamine nanoparticles allows for efficient drug delivery and imaging capabilities, while the biomimetic coating enhances their biocompatibility and targeting ability. These findings contribute valuable insights towards the development of advanced nanomedicine for improved cancer therapeutics.
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Hipertermia Induzida , Nanopartículas , Neoplasias , Humanos , Medicina de Precisão , Biomimética , Doxorrubicina/farmacologia , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Fototerapia/métodos , Sistemas de Liberação de Medicamentos/métodos , Imageamento por Ressonância Magnética , Ferro , Nanomedicina TeranósticaRESUMO
Various types of nanoparticles (NPs) have been widely investigated recently and applied in areas such as industry, the energy sector, and medicine, presenting the risk of their release into the environment. The ecotoxicity of NPs depends on several factors such as their shape and surface chemistry. Polyethylene glycol (PEG) is one of the most often used compounds for functionalisation of NP surfaces, and its presence on the surfaces of NPs may affect their ecotoxicity. Therefore, the present study aimed to assess the influence of PEG modification on the toxicity of NPs. As biological model, we chose freshwater microalgae, a macrophyte and invertebrates, which to a considerable extent enable the assessment of the harmfulness of NPs to freshwater biota. SrF2:Yb3+,Er3+ NPs were used to represent the broad group of up-converting NPs, which have been intensively investigated for medical applications. We quantified the effects of the NPs on five freshwater species representing three trophic levels: the green microalgae Raphidocelis subcapitata and Chlorella vulgaris, the macrophyte Lemna minor, the cladoceran Daphnia magna and the cnidarian Hydra viridissima. Overall, H. viridissima was the most sensitive species to NPs, which affected its survival and feeding rate. In this case, PEG-modified NPs were slightly more toxic than bare ones (non-significant results). No effects were observed on the other species exposed to the two NPs at the tested concentrations. The tested NPs were successfully imaged in the body of D. magna using confocal microscopy; both NPs were detected in the D. magna gut. The results obtained reveal that SrF2:Yb3+,Er3+ NPs can be toxic to some aquatic species; however, the structures have low toxicity effects for most of the tested species.
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Chlorella vulgaris , Elementos da Série dos Lantanídeos , Nanopartículas , Poluentes Químicos da Água , Animais , Organismos Aquáticos , Elementos da Série dos Lantanídeos/farmacologia , Poluentes Químicos da Água/toxicidade , Nanopartículas/toxicidade , DaphniaRESUMO
Understanding the interplay between nanoparticles (NPs) and cells is essential to designing more efficient nanomedicines. Previous research has shown the role of the cell cycle having impact on the efficiency of cellular uptake and accumulation of NPs. However, there is a limited investigation into the biological fate of NPs in cells that are permanently withdrawn from the cell cycle. Here we utilize senescent WI-38 fibroblasts, which do not divide and provide a definitive model for tracking the biological fate of silica nanoparticles (SiNPs) independent of cell cycle. We use several methods to measure the cellular uptake kinetics and intracellular retention of SiNPs, including confocal laser scanning microscopy (CLSM), flow cytometry, and transmission electron microscopy (TEM). We demonstrate that SiNPs readily enter into senescent cells. Once internalized, SiNPs do not exit and accumulate in the cytoplasm for long term. Our study provides a basis for future development of NP-based tools that can detect and target senescent cells for therapy.
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Nanopartículas , Dióxido de Silício , Sobrevivência Celular , Transporte Biológico , FibroblastosRESUMO
The right choice of synthesis route for upconverting nanoparticles (UCNPs) is crucial for obtaining a well-defined product with a specific application capability. Thus we decided to compare the physicochemical, cytotoxic, and temperature-sensing properties of UCNPs obtained from different rare earth (RE) ions, which has been made for the first time in a single study. The core/shell NaYF4:Yb3+,Er3+/NaYF4 UCNPs were obtained by reaction in a mixture of oleic acid and octadecene, and their highly stable water colloids were prepared using the ligand-free modification method. Both oleate-capped and ligand-free UCNPs exhibited a bright upconversion emission upon 975 nm excitation. Moreover, slope values, emission quantum yields, and luminescence lifetimes confirmed an effective energy transfer between the Yb3+ and Er3+ ions. Additionally, the water colloids of the UCNPs showed temperature-sensing properties with a good thermal sensitivity level, higher than 1 % K-1 at 358 K. Evaluation of the cytotoxicity profiles of the obtained products indicated that cell viability was decreased in a dose-dependent manner in the analyzed concentration range.
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Nanopartículas , Ácido Oleico , Luminescência , Análise Espectral , TemperaturaRESUMO
The development of multifunctional drug delivery systems combining two or more nanoparticle-mediated therapies for efficient cancer treatment is highly desired. To face this challenge, a photothermally active polydopamine (PDA) nanoparticle-based platform was designed for the loading of chemotherapeutic drug and targeting of cancer cells. PDA spheres were first functionalized with polyamidoamine (PAMAM) dendrimers followed by the conjugation with polyethylene glycol (PEG) moieties and folic acid (FA) targeting ligand. The anticancer drug doxorubicin (DOX) was then absorbed on the particle surface. We performed the physico-chemical characterization of this versatile material and we assessed further its possible application in chemo- and photothermal therapy using liver cancer cell model. These nanoparticles exhibited high near-infrared photothermal conversion efficacy and allowed for loading of the drug, which upon release in specifically targeted cancer cells suppressed their growth. Using cell proliferation, membrane damage, apoptosis, and oxidative stress assays we demonstrated high performance of this nanosystem in cancer cell death induction, providing a novel promising approach for cancer therapy.
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Antineoplásicos/administração & dosagem , Dendrímeros/química , Portadores de Fármacos/química , Indóis/administração & dosagem , Nanopartículas/química , Terapia Fototérmica , Poliaminas/química , Polímeros/administração & dosagem , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Terapia Combinada , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Estresse Oxidativo/efeitos dos fármacos , Terapia Fototérmica/métodosRESUMO
Glioma belongs to the most aggressive and lethal types of cancer. Glioblastoma multiforme (GBM), the most common type of malignant gliomas, is characterized by a poor prognosis and remains practically incurable despite aggressive treatment such as surgery, radiotherapy, and chemotherapy. Brain tumor cells overexpress a number of proteins that play a crucial role in tumorigenesis and may be exploited as therapeutic targets. One such target can be an extracellular matrix glycoprotein-tenascin-C (TN-C). Downregulation of TN-C by RNA interference (RNAi) is a very promising strategy in cancer therapy. However, the successful delivery of naked double-stranded RNA (dsRNA) complementary to TN-C sequence (ATN-RNA) requires application of delivery vehicles that can efficiently overcome rapid degradation by nucleases and poor intracellular uptake. Here, we present a protocol for application of MNP@PEI as a carrier for ATN-RNA to GBM cells. The obtained complexes consisted of polyethyleneimine (PEI)-coated magnetic nanoparticles combined with the dsRNA show high efficiency in ATN-RNA delivery, resulting not only in significant TN-C expression level downregulation, but also impairing the tumor cells migration.
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Portadores de Fármacos , Técnicas de Transferência de Genes , Nanopartículas de Magnetita , RNA de Cadeia Dupla/administração & dosagem , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Portadores de Fármacos/química , Expressão Gênica , Terapia Genética/métodos , Humanos , Lipídeos/química , Nanopartículas de Magnetita/química , Interferência de RNA , RNA de Cadeia Dupla/genética , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , TransfecçãoRESUMO
INTRODUCTION: We present a multimodal nanoplatforms for the treatment of hepatocellular carcinoma (HCC) in vitro. The nanoplatforms are based on polydopamine (PDA)-coated magnetite nanoparticles (NPs) and spheres (sMAG) with PAMAM dendrimers and functionalized with NHS-PEG-Mal (N-hydroxysuccinimide-polyethylene glycol-maleimide) linker, which allows their functionalization with a folic acid derivative. The nanomaterials bearing a folic acid-targeting moiety show high efficiency in killing cancer cells in the dual chemo- and photothermal therapy (CT-PTT) of the liver cancer cells in comparison to modalities performed separately. MATERIALS AND METHODS: All materials are characterized in detail with transmission electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, zeta potential and magnetic measurements. Also, photothermal properties were determined under irradiation of nanoparticles with laser beam of 2 W/cm2. The nontoxicity of nanoparticles with doxorubicin and without was checked by WST and LIVE/DEAD assay. Those tests were also used to evaluate materials bearing folic acid and anticancer drug in combined chemo- and photothermal therapy of HCC. Further, the generation of reactive oxygen species profile was also evaluated using flow cytometry test. RESULTS: Both NPs and sMAG showed high photothermal properties. Nevertheless, the higher photothermal response was found for magnetic spheres. Materials of concentration above 10 µg/mL reveal that their activity was comparable to free doxorubicin. It is worth highlighting that a functionalized magnetic sphere with DOXO more strongly affected the HepG2 cells than smaller functionalized nanoparticles with DOXO in the performed chemotherapy. This can be attributed to the larger size of particles and a different method of drug distribution. In the further stage, both materials were assessed in combined chemo- and photothermal therapy (CT-PTT) which revealed that magnetic spheres were also more effective in this modality than smaller nanoparticles. CONCLUSION: Here, we present two types of nanomaterials (nanoparticles and spheres) based on polydopamine and PAMAM dendrimers g.5.0 functionalized with NHS-PEG-Mal linker terminated with folic acid for in vitro hepatocellular carcinoma treatment. The obtained materials can serve as efficient agents for dual chemo- and photothermal therapy of HCC. We also proved that PDA-coated magnetic spheres were more efficient in therapies based on near-infrared irradiation because determined cell viabilities for those materials are lower than for the same concentrations of nanomaterials based on small magnetic nanoparticles.
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Antineoplásicos/química , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/terapia , Portadores de Fármacos/química , Neoplasias Hepáticas/terapia , Nanopartículas de Magnetita/química , Fototerapia , Animais , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Linhagem Celular Tumoral , Terapia Combinada , Dendrímeros/química , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Liberação Controlada de Fármacos , Humanos , Indóis/química , Neoplasias Hepáticas/tratamento farmacológico , Polietilenoglicóis/química , Polímeros/químicaRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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The intensive development and commercialization of genetically modified plants observed over the last decade has led to the development of transgenic detection methods that are rapid and sensitive. Among the strategies used for the detection/monitoring of genetically modified organisms (GMOs), surface plasmon resonance (SPR) meets the necessary criteria. This optical technique measures the changes in the refractive index in the vicinity of thin metal layers (i.e., gold) in response to biomolecular interactions occurring at a flat metalâsolution interface. Additionally, it allows the application of functionalized gold nanoparticles (AuNPs) in SPR research to enhance the signal intensity. In the present study, an SPR method, enhanced by the application of AuNPs, was developed to detect transgenic tobacco plants carrying a Streptococcus mutans antigen. The basis for the detection of the target DNA was the hybridization between the genomic DNA isolated from the leaves, stems, and roots of the transgenic tobacco and the biotinylated oligonucleotide probes immobilized onto a streptavidin (SA) sensor chip. SA-functionalized AuNPs coated with a second type of biotinylated probe were applied to increase the sensitivity of the detection method. Analysis of the results indicated that the constructed SPR-based sensor chip can potentially recognize complementary standard fragments (nonamplified genomic DNA) at concentrations as low as 1 pM. Thus, nonamplified transgenic DNA was detected using a label-free and real-time AuNPs-enhanced SPR biosensing method. This unique approach could be used to detect GMOs with high efficiency, even at a low detection limit, high repeatability, and with less time and a lower cost needed for each analysis.
Assuntos
Técnicas Biossensoriais , Plantas Geneticamente Modificadas/genética , Ouro/química , Nanopartículas Metálicas/química , Hibridização de Ácido Nucleico , Streptococcus mutans/genética , Ressonância de Plasmônio de SuperfícieRESUMO
For a number of years nanomaterials have been continuously devised and comprehensively investigated because of the growing demand for them and their multifarious applications, especially in medicine. This paper reports on the properties of SrF2 nanoparticles (NPs) for applications in biomedicine, showing effective ways of their synthesis and luminescence under near infrared radiation - upconversion. NPs doped with lanthanide, Ln3+ ions (where Ln = Yb, Ho, Er, Tm) were prepared by the hydrothermal method and subjected to comprehensive studies, from determination of their structure and morphology, revealing small, 15 nm structures, through spectroscopic properties, to cytotoxicity in vitro. The effects of such factors as the reaction time, type and amount of precipitating compounds and complexing agents on the properties of products were characterized. The cytotoxicity of the synthesized and functionalized NPs was investigated, using human fibroblast cell line (MSU-1.1). The synthesized structures may decrease cells' proliferation in a dose-dependent manner in the measured concentration range (up to 100 µg/mL). However, the cells remain alive according to the fluorescent assay. Moreover, the treated cells were imaged using confocal laser scanning microscopy. Cellular uptake was confirmed by the presence of upconversion luminescence in the cells.
Assuntos
Fibroblastos/efeitos dos fármacos , Fluoretos/química , Nanopartículas/química , Estrôncio/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Química Sintética , Relação Dose-Resposta a Droga , Érbio/química , Fibroblastos/citologia , Fibroblastos/fisiologia , Fluoretos/farmacologia , Hólmio/química , Humanos , Nanopartículas/ultraestrutura , Estrôncio/farmacologia , Túlio/química , Itérbio/químicaRESUMO
The growing incidence of cancer is a problem for modern medicine, since the therapeutic efficacy of applied modalities is still not satisfactory in terms of patients' survival rates, especially in the case of patients with brain tumors. The destructive influence of chemotherapy and radiotherapy on healthy cells reduces the chances of full recovery. With the development of nanotechnology, new ideas on cancer therapy, including brain tumors, have emerged. Photothermal therapy (PTT) is one of these. It utilizes nanoparticles (NPs) that can convert the light, preferably in the near-infrared (NIR) region, into heat. In this paper, we report the use of nanodiamonds (NDs) conjugated with biomimetic polydopamine (PDA) and indocyanine green (ICG) for glioblastoma cancer PTT therapy. The obtained materials were thoroughly analyzed in terms of their PTT effectiveness, as well as their physicochemical properties. The performed research demonstrated that NDs@PDA@ICG can be successfully applied in the photothermal therapy of glioblastoma for PTT and exhibited high photothermal conversion efficiency η above 40%, which is almost 10 times higher than in case of bare NDs. In regard to our results, our material was found to lead to a better therapeutic outcome and higher eradication of glioblastoma cells, as demonstrated in vitro.
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Glioblastoma multiforme (GBM) is the most common type of malignant gliomas, characterized by genetic instability, intratumoral histopathological variability and unpredictable clinical behavior. Disappointing results in the treatment of gliomas with surgery, radiation and chemotherapy have fueled a search for new therapeutic targets and treatment modalities. Here we report new approach towards RNA interference therapy of glioblastoma multiforme based on the magnetic nanoparticles delivery of the double-stranded RNA (dsRNA) with homological sequences to mRNA of tenascin-C (TN-C), named ATN-RNA. The obtained nanocomposite consisted of polyethyleneimine (PEI) coated magnetic nanoparticles conjugated to the dsRNA show high efficiency in ATN-RNA delivery, resulting not only in significant TN-C expression level suppressesion, but also impairing the tumor cells migration. Moreover, synthesized nanomaterials show high contrast properties in magnetic resonance imaging (MRI) and low cytotoxicity combining with lack of induction of interferon response. We believe that the present work is a successful combination of effective, functional, non-immunostimulatory dsRNA delivery system based on magnetic nanoparticles with high potential for further application in GBM therapy.
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Terapia Genética/métodos , Nanopartículas de Magnetita/química , RNA de Cadeia Dupla/química , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Glioblastoma/patologia , Glioblastoma/terapia , Humanos , Imageamento por Ressonância Magnética , Nanopartículas de Magnetita/toxicidade , Polietilenoimina/química , Interferência de RNA , RNA de Cadeia Dupla/metabolismo , RNA Mensageiro/química , RNA Interferente Pequeno/química , RNA Interferente Pequeno/metabolismo , Tenascina/genética , Tenascina/metabolismo , Transfecção/métodosRESUMO
Here we report the synthesis of multifunctional nanocarriers based on PAMAM dendrimers generation (G) 4.0, 5.0 and 6.0 fixed to polydopamine (PDA) coated magnetite nanoparticles (Fe3O4). Synthesized nanoplatforms were characterized by transmission electron microscopy (TEM), the electrokinetic (zeta) potential, Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS) and magnetic resonance imaging (MRI). Further, we show as a proof of concept that nanocarriers functionalized with G 5.0 could be successfully applied in combined chemo- and photothermal therapy (CT-PTT) of the liver cancer cells. The cooperative effect of the modalities mentioned above led to higher mortality of cancer cells when compared to their individual performance. Moreover, the performed in vitro studies revealed that the application of dual therapy triggered the desired cell death mechanism-apoptosis. Furthermore, performed tests using Magnetic Resonance Imaging (MRI) showed that our materials have competitive contrast properties. Overall, the functionality of dendrimers has been extended by merging them with magnetic nanoparticles resulting in multifunctional hybrid nanostructures that are promising smart drug delivery system for cancer therapy.
Assuntos
Antibióticos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Dendrímeros/química , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas de Magnetita/química , Antibióticos Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Meios de Contraste/química , Doxorrubicina/química , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Óxido Ferroso-Férrico/química , Células Hep G2 , Humanos , Indóis/química , Raios Infravermelhos , Cinética , Imageamento por Ressonância Magnética/métodos , Nanopartículas de Magnetita/ultraestrutura , Fototerapia/métodos , Polímeros/química , Nanomedicina Teranóstica/métodosRESUMO
Currently marketed drug-eluting stents are non-selective in their anti-restenotic action. New active substance introduction to polymeric stents and vascular grafts can promote early re-endothelialization, crucial in preventing implant restenosis. Additionally, managing material hydrophobicity by blending synthetic polymers limits adverse effects on bulk properties and controls active substance release. However, the influence of hydrophilic synthetic polymer on human cells in the cardiovascular system remains to be determined. In this report, effects of both poly(ε-caprolactone) (PCL) fibers hydrophilization with Pluronic P123 (P123) and cilostazol (CIL) loading were studied. Physicochemical and mechanical properties of electrospun tubular structures produced from PCL and PCL/P123 fibers with and without CIL were investigated and compared. Release profiles studies and in vitro cell proliferation assays of electrospun materials were conducted. It was found that P123 located near the surface of electrospun fibers increased the rate of CIL release. PCL formulation sustained human umbilical vein endothelial cells (HUVEC) growth for 48â¯h. Despite improved hydrophilicity, PCL/P123 formulations were found to reduce HUVEC viability. Both PCL and PCL/P123 materials reduced primary aortic smooth muscle cells (PASM) viability after 48â¯h. In PCL formulations containing CIL, drug release caused a decrease in PASM viability. P123 blending with PCL was found to be as a useful pre-fabrication technique for modulating surface hydrophobicity of electrospun materials and the release profile of incorporated active substance. The cytotoxicity of P123 was evaluated to improve the design of drug-loaded vascular grafts for cardiovascular applications.
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Sistema Cardiovascular/efeitos dos fármacos , Cilostazol/química , Liberação Controlada de Fármacos/efeitos dos fármacos , Poloxaleno/química , Poliésteres/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Músculo Liso Vascular/efeitos dos fármacos , Tamanho da Partícula , Poloxaleno/farmacologia , Propriedades de SuperfícieRESUMO
Polydopamine (PDA)-coated magnetic nanoparticles functionalized with mono-6-thio-ß-cyclodextrin (SH-ßCD) were obtained and characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), Nuclear and Magnetic Resonance Imaging (NMR and MRI), and doxorubicin (DOXO)-loading experiments. The liver cancer cellular internalization of DOXO-loaded nanoparticles was investigated by confocal imaging microscopy. Synthesized nanomaterials bearing a chemotherapeutic drug and a layer of polydopamine capable of absorbing near-infrared light show high performance in the combined chemo- and photothermal therapy (CT-PTT) of liver cancer due to the synergistic effect of both modalities as demonstrated in vitro. Moreover, our material exhibits improved T2 contrast properties, which have been verified using Carr-Purcell-Meiboom-Gill pulse sequence and MRI Spin-Echo imaging of the nanoparticles dispersed in the agarose gel phantoms. Therefore, the presented results cast new light on the preparation of polydopamine-based magnetic theranostic nanomaterials, as well as on the proper methodology for investigation of magnetic nanoparticles in high field MRI experiments. The prepared material is a robust theranostic nanoasystem with great potential in nanomedicine.
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Low environmental stability of ZnO nanostructures in hydrophilic systems is a crucial factor limiting their practical applications. ZnO nanomaterials need surface passivation with different water-insoluble compounds. This study describes a one-step passivation process of polycrystalline ZnO films with ZnS as a facile method of ZnO surface coating. A simple sulfidation reaction was carried out in gas-phase H2S and it resulted in formation of a ZnS thin layer on the ZnO surface. The ZnS layer not only inhibited the ZnO dissolving process in water but additionally improved its mechanical and electrical properties. After the passivation process, ZnO/ZnS films remained stable in water for over seven days. The electrical conductivity of the ZnO films increased about 500-fold as a result of surface defect passivation and the removal of oxygen molecules which can trap free carriers. The nanohardness and Young's modulus of the samples increased about 64% and 14%, respectively after the ZnS coating formation. Nanowear tests performed using nanoindentation methods revealed reduced values of surface displacements for the ZnO/ZnS system. Moreover, both ZnO and ZnO/ZnS films showed antimicrobial properties against Escherichia coli.
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The chemical composition of nanoparticles (NPs) may be so designed as to provide measurability for numerous imaging techniques in order to achieve synergistic advantages. Innovative and unique structure of the core/shell ZnO@Gd2O3 NPs possesses luminescent and magnetic properties, and is expected that they will become a new generation of contrast agents for Magnetic Resonance Imaging (MRI) and nanocarriers for theranostics. Thus, by surface biofunctionalization, it is possible to indicate particular nanoparticle compositions which provide efficient imaging, targeted drug delivery, and biocompatibility. Novel ZnO@Gd2O3 NPs were synthesized and biofunctionalized by folic acid (FA) and doxorubicin (Doxo) to provide target and anticancer functions. Physicochemical analyses of the nanoparticles were performed. The biological study included a cytotoxicity in vitro, cellular distribution evaluation, as well as toxicity analyses, performed for the first time, on the in vivo zebrafish (Danio rerio) model. Nanoparticles were found to be effective double-function biomarkers (MRI T2 contrast agents, fluorescent imaging). The biological study showed that ZnO@Gd2O3 and ZnO@Gd2O3@OA-polySi@FA NPs are biocompatible in a particular concentration ranges. Conjugation with folic acid and/or doxorubicin resulted in effective drug delivery targeting. The in vivo results described the toxicology profile toward the zebrafish embryo/larvae, including new data concerning the survival, hatching ratio, and developmental malformations.
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Nanopartículas Metálicas , Fenômenos Químicos , Meios de Contraste , Doxorrubicina , Sistemas de Liberação de Medicamentos , Gadolínio , Magnetismo , Óxido de ZincoRESUMO
Synthesis of magnetic nanoparticles and magnetic nanoclusters was performed by the co-precipitation method or solvothermal synthesis, respectively, followed by oxidative polymerization of dopamine, resulting in a polydopamine (PDA) shell. The nanomaterials obtained were described using TEM, FTIR and magnetic measurements. For the first time, cyto- and genotoxicity studies of polydopamine-coated nanostructures were performed on cancer and normal cell lines, providing in-depth insight into the toxicity of such materials. The tests conducted, e.g. ROS, apoptosis and DNA double-break of the nanomaterials obtained revealed the low toxicity of these structures. Thus, these results prove the biocompatibility and low genotoxicity of these materials and provide new data on the toxicity of PDA-coated materials, which is of great importance for their biomedical application.
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Indóis/toxicidade , Nanopartículas de Magnetita/toxicidade , Polímeros/toxicidade , Apoptose/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Dano ao DNA , Humanos , Fenômenos Magnéticos , Nanopartículas de Magnetita/ultraestrutura , Microscopia Eletrônica de Transmissão , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Metallic nanoparticles, in particular gold nanoparticles (AuNPs), offer a wide spectrum of applications in biomedicine. A crucial issue is their cytotoxicity, which depends greatly on various factors, including morphology of nanoparticles. Because metallic nanoparticles have an effect on cell membrane integrity, their shape and size may affect the viability of cells, due to their different geometries as well as physical and chemical interactions with cell membranes. Variations in the size and shape of gold nanoparticles may indicate particular nanoparticle morphologies that provide strong cytotoxicity effects. Synthesis of different sized and shaped bare AuNPs was performed with spherical (~ 10 nm), nanoflowers (~ 370 nm), nanorods (~ 41 nm), nanoprisms (~ 160 nm) and nanostars (~ 240 nm) morphologies. These nanostructures were characterized and interacting with cancer (HeLa) and normal (HEK293T) cell lines and cell viability tests were performed by WST-1 tests and fluorescent live/dead cell imaging experiments. It was shown that various shapes and sizes of gold nanostructures may affect the viability of the cells. Gold nanospheres and nanorods proved to be more toxic than star, flower and prism gold nanostructures. This may be attributed to their small size and aggregation process. This is the first report concerning a comparison of cytotoxic profile in vitro with a wide spectrum of bare AuNPs morphology. The findings show their possible use in biomedical applications.