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1.
Sci Rep ; 14(1): 13015, 2024 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844752

RESUMO

Calcium hydroxide (Ca(OH)2NPs), calcium titanate (CaTiO3NPs) and yttrium oxide (Y2O3NPs) nanoparticles are prevalent in many industries, including food and medicine, but their small size raises concerns about potential cellular damage and genotoxic effects. However, there are very limited studies available on their genotoxic effects. Hence, this was done to investigate the effects of multiple administration of Ca(OH)2NPs, CaTiO3NPs or/and Y2O3NPs on genomic DNA stability, mitochondrial membrane potential integrity and inflammation induction in mouse brain tissues. Mice were orally administered Ca(OH)2NPs, CaTiO3NPs or/and Y2O3NPs at a dose level of 50 mg/kg b.w three times a week for 2 weeks. Genomic DNA integrity was studied using Comet assay and the level of reactive oxygen species (ROS) within brain cells was analyzed using 2,7 dichlorofluorescein diacetate dye. The expression level of Presenilin-1, tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) genes and the integrity of the mitochondrial membrane potential were also detected. Oral administration of Ca(OH)2NPs caused the highest damage to genomic DNA and mitochondrial membrane potential, less genomic DNA and mitochondrial damage was induced by CaTiO3NPs administration while administration of Y2O3NPs did not cause any remarkable change in the integrity of genomic DNA and mitochondrial membrane potential. Highest ROS generation and upregulation of presenilin-1, TNF-α and IL-6 genes were also observed within the brain cells of mice administrated Ca(OH)2NPs but Y2O3NPs administration almost caused no changes in ROS generation and genes expression compared to the negative control. Administration of CaTiO3NPs alone slightly increased ROS generation and the expression level of TNF-α and IL-6 genes. Moreover, no remarkable changes in the integrity of genomic DNA and mitochondrial DNA potential, ROS level and the expression level of presenilin-1, TNF-α and IL-6 genes were noticed after simultaneous coadministration of Y2O3NPs with Ca(OH)2NPs and CaTiO3NPs. Coadministration of Y2O3NPs with Ca(OH)2NPs and CaTiO3NPs mitigated Ca(OH)2NPs and CaTiO3NPs induced ROS generation, genomic DNA damage and inflammation along with restoring the integrity of mitochondrial membrane potential through Y2O3NPs scavenging free radicals ability. Therefore, further studies are recommended to study the possibility of using Y2O3NPs to alleviate Ca(OH)2NPs and CaTiO3NPs induced genotoxic effects.


Assuntos
Hidróxido de Cálcio , Dano ao DNA , Inflamação , Potencial da Membrana Mitocondrial , Nanopartículas , Espécies Reativas de Oxigênio , Titânio , Ítrio , Animais , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Dano ao DNA/efeitos dos fármacos , Hidróxido de Cálcio/farmacologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Titânio/química , Titânio/toxicidade , Inflamação/metabolismo , Inflamação/patologia , Ítrio/química , Nanopartículas/química , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Masculino , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , DNA Mitocondrial/metabolismo
2.
Anal Chem ; 96(19): 7697-7705, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38697043

RESUMO

Dual/multimodal imaging strategies are increasingly recognized for their potential to provide comprehensive diagnostic insights in cancer imaging by harnessing complementary data. This study presents an innovative probe that capitalizes on the synergistic benefits of afterglow luminescence and magnetic resonance imaging (MRI), effectively eliminating autofluorescence interference and delivering a superior signal-to-noise ratio. Additionally, it facilitates deep tissue penetration and enables noninvasive imaging. Despite the advantages, only a limited number of probes have demonstrated the capability to simultaneously enhance afterglow luminescence and achieve high-resolution MRI and afterglow imaging. Herein, we introduce a cutting-edge imaging platform based on semiconducting polymer nanoparticles (PFODBT) integrated with NaYF4@NaGdF4 (Y@Gd@PFO-SPNs), which can directly amplify afterglow luminescence and generate MRI and afterglow signals in tumor tissues. The proposed mechanism involves lanthanide nanoparticles producing singlet oxygen (1O2) upon white light irradiation, which subsequently oxidizes PFODBT, thereby intensifying afterglow luminescence. This innovative platform paves the way for the development of high signal-to-background ratio imaging modalities, promising noninvasive diagnostics for cancer.


Assuntos
Elementos da Série dos Lantanídeos , Imageamento por Ressonância Magnética , Nanopartículas , Polímeros , Semicondutores , Imageamento por Ressonância Magnética/métodos , Animais , Elementos da Série dos Lantanídeos/química , Polímeros/química , Nanopartículas/química , Camundongos , Humanos , Gadolínio/química , Luminescência , Oxigênio Singlete/química , Ítrio/química , Fluoretos/química , Camundongos Nus
3.
Photobiomodul Photomed Laser Surg ; 42(5): 343-349, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38579157

RESUMO

Objective: This in vitro study evaluates the shear bond strength (SBS) of yttria-stabilized tetragonal zirconia (Y-TZP) and resin cement after different surface treatments. Materials and methods: Forty-eight ceramic cubes were divided into four groups (n = 12): G1 (control) sandblasting with Al2O3; G2-sandblasting with silica-coated Al2O3 (Rocatec); G3-Rocatec + CO2 laser; and G4-CO2 laser + Rocatec. A metallic primer was applied to the pretreated ceramic. A rubber ring was adapted on the central area, and then, the resin cement was inserted into the matrix and photoactivated. The samples were evaluated regarding surface roughness (Ra), SBS, failure type, and qualitatively with scanning electron microscopy (SEM). The data were analyzed by one-way analysis of variance followed by Tukey's test (p < 0.05). Results: The mean values of Ra (µm) were as follows: G1-4.52a, G2-4.24a,b, G3-4.10a,b, and G4-2.90b and the mean values of SBS (MPa) were as follows: G1-7.84a , G2-4.41b , G3-4.61b and G4-6.14a,b. SEM analyses showed superficial irregularities for all groups, being more prominent for G1. The presence of silica deposits was observed for G2, G3, and G4, but in the last two groups there were some linear areas, promoted by the fusion of silica, due to the thermomechanical action of the CO2 laser. Conclusions: The surface treatment with CO2 laser + Rocatec, using one MDP-based cement, can be an alternative protocol for the adhesion cementation of Y-TZP ceramic since it was as effective as the conventional pretreatment with aluminum oxide sandblasting.


Assuntos
Cerâmica , Colagem Dentária , Teste de Materiais , Microscopia Eletrônica de Varredura , Cimentos de Resina , Resistência ao Cisalhamento , Propriedades de Superfície , Ítrio , Zircônio , Zircônio/química , Ítrio/química , Cimentos de Resina/química , Cerâmica/química , Colagem Dentária/métodos , Lasers de Gás , Técnicas In Vitro , Dióxido de Silício/química , Óxido de Alumínio/química
4.
J Biomed Mater Res B Appl Biomater ; 111(10): 1824-1839, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37255008

RESUMO

Although yttria-stabilized tetragonal zirconia polycrystals (Y-TZP) ceramics have been widely used as restorative materials due to their high mechanical strength, unique esthetic effect, and good biocompatibility, their general application to implant materials is still limited by their biological inertness and hydrothermal aging phenomenon. Existing studies have attempted to investigate how to enhance the bioactivity or hydrothermal aging resistance of Y-TZP. Still, more studies need to be done on the modification that combines these two aspects. In this study, Y-TZP was prepared by 77S bioactive glass (BG) sol and akermanite (AKT) sol infiltration and microwave sintering, which provided Y-TZP with high bioactivity while maintaining resistance to hydrothermal aging. Results of phase composition evaluation, microstructural characteristics, and mechanical property tests showed that modified Y-TZP specimens exhibited little or no tetragonal-to-monoclinic (t → m) transformation and maintained relatively high mechanical properties after accelerated hydrothermal aging treatment. The in vitro biological behaviors showed that the introduction of 77S BG and AKT significantly promoted cell adhesion, spreading, viability, and proliferation on the surface of modified Y-TZP ceramics. Therefore, this modification could effectively enhance the bioactivity and hydrothermal aging resistance of Y-TZP ceramics for its application in dental implant materials.


Assuntos
Implantes Dentários , Proteínas Proto-Oncogênicas c-akt , Teste de Materiais , Propriedades de Superfície , Zircônio/farmacologia , Zircônio/química , Ítrio/química , Cerâmica/farmacologia , Cerâmica/química , Materiais Dentários
5.
Inorg Chem ; 61(44): 17527-17536, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36281990

RESUMO

Utilizing a choice of α,ω-oligosilanylene diides, it is possible to synthesize a number of heterocyclosilanes with heteroelements of calcium, yttrium, and iron by metathesis reactions with respective metal halides CaI2, YCl3, and FeBr2. 29Si NMR spectroscopic analysis of the calcacyclosilanes suggests that these compounds retain a strong oligosilanylene dianion character, which is more pronounced than in the analogous magnesacyclosilanes. As the electronegativity of calcium lies between potassium and magnesium, silyl calcium reagents should be considered as building blocks with an attractive reactivity profile. Reaction of a 1,4-oligosilanylene diide with YCl3 gave the five-membered yttracyclosilane as an ate-complex with two chlorides still attached to the yttrium atom. Reaction of the obtained compound with two equivalents of NaCp led to another five-membered yttracyclosilane ate-complex with an yttracene fragment. When using a dianionic oligosilanylene ligand containing a siloxane unit, the siloxane oxygen acted as an additional coordination site for Ca and Y. When the same ligand was used to prepare a cyclic 1-ferra-4-oxatetrasilacyclohexane, an analogous transannular interaction between the iron and oxygen atoms is missing.


Assuntos
Ferro , Ítrio , Ferro/química , Ítrio/química , Cálcio/química , Ligantes , Siloxanas/química , Oxigênio
6.
Molecules ; 27(9)2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35566114

RESUMO

Upconverting nanoparticles have unique spectral and photophysical properties that make them suitable for development of theranostics for imaging and treating large and deep-seated tumors. Nanoparticles based on NaYF4 crystals doped with lanthanides Yb3+ and Er3+ were obtained by the high-temperature decomposition of trifluoroacetates in oleic acid and 1-octadecene. Such particles have pronounced hydrophobic properties. Therefore, to obtain stable dispersions in aqueous media for the study of their properties in vivo and in vitro, the polyethylene glycol (PEG)-glycerolipids of various structures were obtained. To increase the circulation time of PEG-lipid coated nanoparticles in the bloodstream, long-chain substituents are needed to be attached to the glycerol backbone using ether bonds. To prevent nanoparticle aggregation, an L-cysteine-derived negatively charged carboxy group should be included in the lipid molecule.


Assuntos
Nanopartículas , Polietilenoglicóis , Cisteína , Fluoretos/química , Nanopartículas/química , Ácido Oleico , Polietilenoglicóis/química , Ítrio/química
7.
Int J Mol Sci ; 23(6)2022 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-35328427

RESUMO

Plasma surface treatment can be an attractive strategy for modifying the chemically inert nature of zirconia to improve its clinical performance. This study aimed to clarify the effect of plasma gas compositions on the physicochemical surface modifications of 3 mol% yttria-stabilized zirconia (3Y-TZP). The cold, atmospheric plasma discharges were carried out by using four different plasma gases, which are He/O2, N2/Ar, N2, and Ar from an application distance of 10 mm for 60 s. Static contact angles were measured to define the surface free energy. Changes in elemental composition, surface crystallinity, and surface topography were assessed with X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), confocal laser scanning microscopy (CLSM), and scanning electron microscopy (SEM), respectively. A significant decrease in water contact angle was observed in all plasma groups with the lowest value of 69° in the N2/Ar group. CLSM and SEM investigations exhibited no morphological changes in all plasma groups. XPS revealed that a reduction in the surface C content along with an increase in O content was pronounced in the case of N2/Ar compared to others, which was responsible for high hydrophilicity of the surface. XRD showed that the changes in crystallite size and microstrain due to oxygen atom displacements were observed in the N2/Ar group. The N2/Ar plasma treatment may contribute to enhancing the bioactivity as well as the bonding performance of 3Y-TZP by controlling the plasma-generated nitrogen functionalities.


Assuntos
Gases em Plasma , Ítrio , Cerâmica/química , Teste de Materiais , Microscopia Eletrônica de Varredura , Propriedades de Superfície , Difração de Raios X , Ítrio/química , Zircônio/química
8.
J Toxicol Environ Health A ; 85(4): 131-142, 2022 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-34612163

RESUMO

Melanoma is the most aggressive type of skin cancer, and thus it is important to develop new drugs for its treatment. The present study aimed to examine the antitumor effects of solamargine a major alkaloid heteroside present in Solanum lycocarpum fruit. In addition solamargine was incorporated into nanoparticles (NP) of yttrium vanadate functionalized with 3-chloropropyltrimethoxysilane (YVO4:Eu3+:CPTES:SM) to determine antitumor activity. The anti-melanoma assessment was performed using a syngeneic mouse melanoma model B16F10 cell line. In addition, systemic toxicity, nephrotoxic, and genotoxic parameters were assessed. Solamargine, at doses of 5 or 10 mg/kg/day administered subcutaneously to male C57BL/6 mice for 5 days, decreased tumor size and frequency of mitoses in tumor tissue, indicative of a decrease in cell proliferation. Treatments with YVO4:Eu3+:CPTES:SM significantly reduced the number of mitoses in tumor tissue, associated with no change in tumor size. There were no apparent signs of systemic toxicity, nephrotoxicity, and genotoxicity initiated by treatments either with solamargine alone or plant alkaloid incorporated into NP. The animals treated with YVO4:Eu3+:CPTES:SM exhibited significant increase in spleen weight accompanied by no apparent histological changes in all tissues examined. In addition, animals treated with solamargine (10 mg/kg/day) and YVO4:Eu3+:CPTES:SM demonstrated significant reduction in hepatic DNA damage which was induced by tumor growth. Therefore, data suggest that solamargine may be considered a promising candidate in cancer therapy with no apparent toxic effects.


Assuntos
Antineoplásicos/farmacologia , Melanoma Experimental/tratamento farmacológico , Alcaloides de Solanáceas/farmacologia , Animais , Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Dano ao DNA , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitose/efeitos dos fármacos , Nanopartículas/administração & dosagem , Silanos/química , Alcaloides de Solanáceas/toxicidade , Ítrio/química
9.
ACS Appl Mater Interfaces ; 14(1): 57-68, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-34935343

RESUMO

Integrating chemodynamic therapy (CDT) and photodynamic therapy (PDT) into one nanoplatform can produce much more reactive oxygen species (ROS) for tumor therapy. Nevertheless, it is still a great challenge to selectively generate sufficient ROS in tumor regions. Meanwhile, CDT and PDT are restricted by insufficient H2O2 content in the tumor as well as by the limited tumor tissue penetration of the light source. In this study, a smart pH/ROS-responsive nanoplatform, Fe2+@UCM-BBD, is rationally designed for tumor combination therapy. The acidic microenvironment can induce the pH-responsive release of doxorubicin (DOX), which can induce tumor apoptosis through DNA damage. Beyond that, DOX can promote the production of H2O2, providing sufficient materials for CDT. Of note, upconversion nanoparticles at the core can convert the 980 nm light to red and green light, which are used to activate Ce6 to produce singlet oxygen (1O2) and achieve upconversion luminescence imaging, respectively. Then, the ROS-responsive linker bis-(alkylthio)alkene is cleaved by 1O2, resulting in the release of Fenton reagent (Fe2+) to realize CDT. Taken together, Fe2+@UCM-BBD exhibits on-demand therapeutic reagent release capability, excellent biocompatibility, and remarkable tumor inhibition ability via synergistic chemo/photodynamic/chemodynamic combination therapy.


Assuntos
Antineoplásicos/uso terapêutico , Doxorrubicina/uso terapêutico , Portadores de Fármacos/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Clorofilídeos/química , Clorofilídeos/efeitos da radiação , Clorofilídeos/uso terapêutico , Terapia Combinada , Doxorrubicina/química , Portadores de Fármacos/química , Portadores de Fármacos/efeitos da radiação , Liberação Controlada de Fármacos , Tratamento Farmacológico , Érbio/química , Érbio/efeitos da radiação , Érbio/uso terapêutico , Feminino , Fluoretos/química , Fluoretos/efeitos da radiação , Fluoretos/uso terapêutico , Humanos , Ferro/química , Ferro/efeitos da radiação , Ferro/uso terapêutico , Nanopartículas Metálicas/química , Nanopartículas Metálicas/efeitos da radiação , Camundongos Endogâmicos BALB C , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Itérbio/química , Itérbio/efeitos da radiação , Itérbio/uso terapêutico , Ítrio/química , Ítrio/efeitos da radiação , Ítrio/uso terapêutico
10.
Microbiol Spectr ; 9(3): e0136421, 2021 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-34908455

RESUMO

Sporotrichosis is a deep fungal infection caused by Sporothrix species. Currently, itraconazole is the main treatment, but fungal resistance, adverse effects, and drug interactions remain major concerns, especially in patients with immune dysfunction. Therefore, an alternative treatment is greatly in demand. This animal study aimed to investigate the inhibitory effect of neodymium-doped yttrium aluminum garnet (Nd:YAG) 1,064-nm laser treatment on Sporothrix globosa and to explore whether it happens through regulation of the Nod-like receptor thermoprotein domain-related protein 3 (NLRP3)/caspase-1 pyroptosis and apoptosis pathway. After laser irradiation, a series of studies, including assays of viability (using the cell counting kit-8 [CCK-8]), morphological structure changes, reactive oxygen species (ROS) accumulation, mitochondrial membrane potential, oxidative stress, cell cycle progression, and metacaspase activation, were conducted to estimate the effect of Nd:YAG 1,064-nm laser treatment on Sporothrix globosa cell apoptosis in vitro. For in vivo studies, mice were infected with S. globosa and then treated with laser or itraconazole, and their footpad skin lesions and the changes in the histology of tissue samples were compared. In addition, changes in the levels of NLRP3, caspase-1, and caspase-3 were assessed by immunohistochemistry, while the levels of interleukin 17 (IL-17), interferon gamma (IFN-γ), and transforming growth factor ß1 (TGF-ß1) in peripheral blood were tested by enzyme-linked immunosorbent assay (ELISA). The in vitro growth of S. globosa was inhibited and apoptosis was observed after laser treatment. According to the in vivo studies, the efficacy of the laser treatment was similar to that of itraconazole. Moreover, the NLRP3/caspase-1 pyroptosis pathway was activated, with a Th1/Th17 cell response, and the expression of caspase-3 was also upregulated. Nd:YAG 1,064-nm laser treatment can effectively inhibit the growth of S. globosa by activating fungal apoptosis and pyroptosis through the NLRP3/caspase-1 pathway. Therefore, Nd:YAG 1,064-nm laser irradiation is an alternative for sporotrichosis therapy. IMPORTANCE Nd:YAG 1,064-nm laser irradiation is a useful alternative for the treatment of sporotrichosis, especially in patients with liver dysfunction, pregnant women, and children, for whom the administration of antifungal drugs is not suitable. It may improve the overall treatment effect by shortening the duration of antifungal treatment and reducing tissue inflammation.


Assuntos
Antifúngicos/uso terapêutico , Apoptose/efeitos da radiação , Itraconazol/uso terapêutico , Lasers de Estado Sólido/uso terapêutico , Piroptose/efeitos da radiação , Esporotricose/terapia , Alumínio/química , Animais , Caspase 1/metabolismo , Ciclo Celular/efeitos da radiação , Feminino , Humanos , Potencial da Membrana Mitocondrial/efeitos da radiação , Camundongos , Camundongos Endogâmicos BALB C , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Neodímio/química , Estresse Oxidativo/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Sporothrix/efeitos dos fármacos , Sporothrix/efeitos da radiação , Células Th1/imunologia , Células Th17/imunologia , Ítrio/química
11.
Sci Rep ; 11(1): 21373, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34725396

RESUMO

Upconverting luminescent lanthanide-doped nanoparticles (UCNP) belong to promising new materials that absorb infrared light able to penetrate in the deep tissue level, while emitting photons in the visible or ultraviolet region, which makes them favorable for bioimaging and cell labeling. Here, we have prepared upconverting NaYF4:Yb,Er@NaYF4:Nd core-shell nanoparticles, which were coated with copolymers of N,N-dimethylacrylamide (DMA) and 2-(acryloylamino)-2-methylpropane-1-sulfonic acid (AMPS) or tert-butyl [2-(acryloylamino)ethyl]carbamate (AEC-Boc) with negative or positive charges, respectively. The copolymers were synthesized by a reversible addition-fragmentation chain transfer (RAFT) polymerization, reaching Mn ~ 11 kDa and containing ~ 5 mol% of reactive groups. All copolymers contained bisphosphonate end-groups to be firmly anchored on the surface of NaYF4:Yb,Er@NaYF4:Nd core-shell nanoparticles. To compare properties of polymer coatings, poly(ethylene glycol)-coated and neat UCNP were used as a control. UCNP with various charges were then studied as labels of carcinoma cells, including human hepatocellular carcinoma HepG2, human cervical cancer HeLa, and rat insulinoma INS-1E cells. All the particles proved to be biocompatible (nontoxic); depending on their ξ-potential, the ability to penetrate the cells differed. This ability together with the upconversion luminescence are basic prerequisites for application of particles in photodynamic therapy (PDT) of various tumors, where emission of nanoparticles in visible light range at ~ 650 nm excites photosensitizer.


Assuntos
Acrilamidas/química , Corantes Fluorescentes/química , Fluoretos/química , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Ítrio/química , Células HeLa , Células Hep G2 , Humanos , Imagem Óptica/métodos
12.
J Mater Chem B ; 9(44): 9213-9220, 2021 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-34698754

RESUMO

Carbon monoxide (CO) can cause mitochondrial dysfunction, inducing apoptosis of cancer cells, which sheds light on a potential alternative for cancer treatment. However, the existing CO-based compounds are inherently limited by their chemical nature, such as high biological toxicity and uncontrolled CO release. Therefore, a nanoplatform - UmPF - that addresses such pain points is urgently in demand. In this study, we have proposed a nanoplatform irradiated by near-infrared (NIR) light to release CO. Iron pentacarbonyl (Fe(CO)5) was loaded in the mesoporous polydopamine layer that was coated on rare-earth upconverting nanoparticles (UCNPs). The absorption wavelength of Fe(CO)5 overlaps with the emission bands of the UCNPs in the UV-visible light range, and therefore the emissions from the UCNPs can be used to incite Fe(CO)5 to control the release of CO. Besides, the catechol groups, which are abundant in the polydopamine structure, serve as an ideal locating spot to chelate with Fe(CO)5; in the meantime, the mesoporous structure of the polydopamine layer improves the loading efficiency of Fe(CO)5 and reduces its biological toxicity. The photothermal effect (PTT) of the polydopamine layer is highly controllable by adjusting the external laser intensity, irradiation time and the thickness of the polydopamine layer. The results illustrate that the combination of CO gas therapy (GT) and polydopamine PTT brought by the final nanoplatform can be synergistic in killing cancer cells in vitro. More importantly, the possible toxic side effects can be effectively prevented from affecting the organism, since CO will not be released in this system without near-infrared light radiation.


Assuntos
Antineoplásicos/farmacologia , Monóxido de Carbono/metabolismo , Corantes Fluorescentes/farmacologia , Nanopartículas Metálicas/química , Antineoplásicos/química , Antineoplásicos/efeitos da radiação , Antineoplásicos/toxicidade , Corantes Fluorescentes/química , Corantes Fluorescentes/efeitos da radiação , Corantes Fluorescentes/toxicidade , Fluoretos/química , Fluoretos/farmacologia , Fluoretos/efeitos da radiação , Fluoretos/toxicidade , Células HeLa , Humanos , Indóis/química , Indóis/farmacologia , Indóis/efeitos da radiação , Indóis/toxicidade , Raios Infravermelhos , Compostos de Ferro/química , Compostos de Ferro/farmacologia , Compostos de Ferro/efeitos da radiação , Compostos de Ferro/toxicidade , Nanopartículas Metálicas/efeitos da radiação , Nanopartículas Metálicas/toxicidade , Microscopia Confocal , Microscopia de Fluorescência , Terapia Fototérmica , Polímeros/química , Polímeros/farmacologia , Polímeros/efeitos da radiação , Polímeros/toxicidade , Porosidade , Túlio/química , Túlio/farmacologia , Túlio/efeitos da radiação , Túlio/toxicidade , Itérbio/química , Itérbio/farmacologia , Itérbio/efeitos da radiação , Itérbio/toxicidade , Ítrio/química , Ítrio/farmacologia , Ítrio/efeitos da radiação , Ítrio/toxicidade
13.
J Am Chem Soc ; 143(36): 14907-14915, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34469145

RESUMO

Chemotherapy can induce toxicity in the central and peripheral nervous systems and result in chronic adverse reactions that impede continuous treatment and reduce patient quality of life. There is a current lack of research to predict, identify, and offset drug-induced neurotoxicity. Rapid and accurate assessment of potential neuropathy is crucial for cost-effective diagnosis and treatment. Here we report dynamic near-infrared upconversion imaging that allows intraneuronal transport to be traced in real time with millisecond resolution, but without photobleaching or blinking. Drug-induced neurotoxicity can be screened prior to phenotyping, on the basis of subtle abnormalities of kinetic characteristics in intraneuronal transport. Moreover, we demonstrate that combining the upconverting nanoplatform with machine learning offers a powerful tool for mapping chemotherapy-induced peripheral neuropathy and assessing drug-induced neurotoxicity.


Assuntos
Transporte Biológico/fisiologia , Substâncias Luminescentes/química , Nanopartículas Metálicas/química , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Síndromes Neurotóxicas/metabolismo , Animais , Antineoplásicos/efeitos adversos , Fluoretos/química , Gânglios Espinais/citologia , Neurônios/efeitos dos fármacos , Paclitaxel/efeitos adversos , Ratos Sprague-Dawley , Máquina de Vetores de Suporte , Túlio/química , Vincristina/efeitos adversos , Itérbio/química , Ítrio/química
14.
ACS Appl Mater Interfaces ; 13(33): 39076-39087, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34378375

RESUMO

Fluorophores with multifunctional properties known as rare-earth-doped nanoparticles (RENPs) are promising candidates for bioimaging, therapy, and drug delivery. When applied in vivo, these nanoparticles (NPs) have to retain long blood-circulation time, bypass elimination by phagocytic cells, and successfully arrive at the target area. Usually, NPs in a biological medium are exposed to proteins, which form the so-called "protein corona" (PC) around the NPs and influence their targeted delivery and accumulation in cells and tissues. Different surface coatings change the PC size and composition, subsequently deciding the fate of the NPs. Thus, detailed studies on the PC are of utmost importance to determine the most suitable NP surface modification for biomedical use. When it comes to RENPs, these studies are particularly scarce. Here, we investigate the PC composition and its impact on the cellular uptake of citrate-, SiO2-, and phospholipid micelle-coated RENPs (LiYF4:Yb3+,Tm3+). We observed that the PC of citrate- and phospholipid-coated RENPs is relatively stable and similar in the adsorbed protein composition, while the PC of SiO2-coated RENPs is larger and highly dynamic. Moreover, biocompatibility, accumulation, and cytotoxicity of various RENPs in cancer cells have been evaluated. On the basis of the cellular imaging, supported by the inhibition studies, it was revealed that RENPs are internalized by endocytosis and that specific endocytic routes are PC composition dependent. Overall, these results are essential to fill the gaps in the fundamental understanding of the nano-biointeractions of RENPs, pertinent for their envisioned application in biomedicine.


Assuntos
Materiais Revestidos Biocompatíveis/química , Corantes Fluorescentes/química , Compostos de Lítio/química , Nanopartículas Metálicas/química , Coroa de Proteína/metabolismo , Dióxido de Silício/química , Ítrio/química , Adsorção , Neoplasias da Mama , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular , Ácido Cítrico/química , Materiais Revestidos Biocompatíveis/metabolismo , Endocitose , Corantes Fluorescentes/metabolismo , Humanos , Tamanho da Partícula , Fosfolipídeos/química , Propriedades de Superfície
15.
J Mater Chem B ; 9(36): 7423-7434, 2021 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-34373887

RESUMO

Over the last decade, upconversion nanoparticles (UCNP) have been widely investigated in nanomedicine due to their high potential as imaging agents in the near-infrared (NIR) optical window of biological tissues. Here, we successfully develop active targeted UCNP as potential probes for dual NIR-NIR fluorescence and radioactive-guided surgery of prostate-specific membrane antigen (PSMA)(+) prostate cancers. We designed a one-pot thermolysis synthesis method to obtain oleic acid-coated spherical NaYF4:Yb,Tm@NaYF4 core/shell UCNP with narrow particle size distribution (30.0 ± 0.1 nm, as estimated by SAXS analysis) and efficient upconversion luminescence. Polyethylene glycol (PEG) ligands bearing different anchoring groups (phosphate, bis- and tetra-phosphonate-based) were synthesized and used to hydrophilize the UCNP. DLS studies led to the selection of a tetra-phosphonate PEG(2000) ligand affording water-dispersible UCNP with sustained colloidal stability in several aqueous media. PSMA-targeting ligands (i.e., glutamate-urea-lysine derivatives called KuEs) and fluorescent or radiolabelled prosthetic groups were grafted onto the UCNP surface by strain-promoted azide-alkyne cycloaddition (SPAAC). These UCNP, coated with 10 or 100% surface density of KuE ligands, did not induce cytotoxicity over 24 h incubation in LNCaP-Luc or PC3-Luc prostate cancer cell lines or in human fibroblasts for any of the concentrations evaluated. Competitive binding assays and flow cytometry demonstrated the excellent affinity of UCNP@KuE for PSMA-positive LNCaP-Luc cells compared with non-targeted UCNP@CO2H. Furthermore, the binding of UCNP@KuE to prostate tumour cells was positively correlated with the surface density of PSMA-targeting ligands and maintained after 125I-radiolabelling. Finally, a preliminary biodistribution study in LNCaP-Luc-bearing mice demonstrated the radiochemical stability of non-targeted [125I]UCNP paving the way for future in vivo assessments.


Assuntos
Antígenos de Superfície/metabolismo , Materiais Revestidos Biocompatíveis/química , Glutamato Carboxipeptidase II/metabolismo , Nanopartículas de Magnetita/química , Animais , Antígenos de Superfície/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/metabolismo , Materiais Revestidos Biocompatíveis/farmacologia , Materiais Revestidos Biocompatíveis/uso terapêutico , Reação de Cicloadição , Fluoretos/química , Glutamato Carboxipeptidase II/química , Humanos , Ligantes , Nanopartículas de Magnetita/uso terapêutico , Nanopartículas de Magnetita/toxicidade , Masculino , Camundongos , Ácidos Oleicos/química , Imagem Óptica , Tamanho da Partícula , Polietilenoglicóis/química , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/cirurgia , Túlio/química , Distribuição Tecidual , Itérbio/química , Ítrio/química
16.
ACS Appl Mater Interfaces ; 13(24): 29070-29082, 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34101411

RESUMO

Two novel stimuli-responsive drug delivery systems (DDSs) were successfully created from bovine serum albumin- or myoglobin-gated upconversion nanoparticle-embedded mesoporous silica nanovehicles (UCNP@mSiO2) via diselenide (Se-Se)-containing linkages. More importantly, multiple roles of each scaffold of the nanovehicles were achieved. The controlled release of the encapsulated drug doxorubicin (DOX) within the mesopores was activated by triple stimuli (acidic pH, glutathione, or H2O2) of tumor microenvironments, owing to the conformation/surface charge changes in proteins or the reductive/oxidative cleavages of the Se-Se bonds. Upon release of DOX, the Förster resonance energy transfer between the UCNP cores and encapsulated DOX was eliminated, resulting in an increase in ratiometric upconversion luminescence for DOX release tracking in real time. The two protein-gated DDSs showed some differences in the drug release performances, relevant to structures and properties of the protein nanogates. The introduction of the Se-Se linkages not only increased the versatility of reductive/oxidative cleavages but also showed less cytotoxicity to all cell lines. The DOX-loaded protein-gated nanovehicles showed the inhibitory effect on tumor growth in tumor-bearing mice and negligible damage/toxicity to the normal tissues. The constructed nanovehicles in a spatiotemporally controlled manner have fascinating prospects in targeted drug delivery for cancer chemotherapy.


Assuntos
Antineoplásicos/uso terapêutico , Doxorrubicina/uso terapêutico , Portadores de Fármacos/química , Nanopartículas Metálicas/química , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/química , Bovinos , Doxorrubicina/química , Portadores de Fármacos/metabolismo , Liberação Controlada de Fármacos , Érbio/química , Feminino , Fluoretos/química , Glutationa/metabolismo , Células HeLa , Humanos , Peróxido de Hidrogênio/metabolismo , Concentração de Íons de Hidrogênio , Camundongos Endogâmicos C57BL , Mioglobina/química , Mioglobina/metabolismo , Porosidade , Soroalbumina Bovina/química , Soroalbumina Bovina/metabolismo , Dióxido de Silício/química , Ensaios Antitumorais Modelo de Xenoenxerto , Itérbio/química , Ítrio/química
17.
Biomolecules ; 11(5)2021 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-34066897

RESUMO

In the present study, biocompatible manganese nanoparticles have been linked with zinc and iron molecules to prepare different derivatives of Mn0.5Zn0.5ErxYxFe2-2xO4 NPs (x = 0.02, 0.04, 0.06, 0.08, 0.10), using an ultrasonication approach. The structure, surface morphology, and chemical compositions of Mn0.5Zn0.5ErxYxFe2-2xO4 NPs were elucidated by X-ray diffractometer (XRD), High-resolution transmission electron microscopy (HR-TEM), scanning electron microscope (SEM), and Energy Dispersive X-Ray Analysis (EDX) techniques. The bioactivity of Mn0.5Zn0.5ErxYxFe2-2xO4 NPs on normal (HEK-293) and (HCT-116) colon cancer cell line was evaluated. The Mn0.5Zn0.5ErxYxFe2-2xO4 NPs treatment post 48 h resulted in a significant reduction in cells (via MTT assay, having an IC50 value between 0.88 µg/mL and 2.40 µg/mL). The specificity of Mn0.5Zn0.5ErxYxFe2-2xO4 NPs were studied by treating them on normal cells line (HEK-293). The results showed that Mn0.5Zn0.5ErxYxFe2-2xO4 NPs did not incur any effect on HEK-293, which suggests that Mn0.5Zn0.5ErxYxFe2-2xO4 NPs selectively targeted the colon cancerous cells. Using Candida albicans, antifungal activity was also studied by evaluating minimum inhibitory/fungicidal concentration (MIC/MFC) and the effect of nanomaterial on the germ tube formation, which exhibited that NPs significantly inhibited the growth and germ tube formation. The obtained results hold the potential to design nanoparticles that lead to efficient bioactivity.


Assuntos
Antifúngicos/farmacologia , Antineoplásicos/farmacologia , Nanopartículas Metálicas/administração & dosagem , Neoplasias/tratamento farmacológico , Óxidos/química , Candida albicans/efeitos dos fármacos , Linhagem Celular Tumoral , Érbio/química , Humanos , Manganês/química , Nanopartículas Metálicas/química , Neoplasias/metabolismo , Neoplasias/patologia , Ondas Ultrassônicas , Ítrio/química , Zinco/química
18.
ACS Appl Bio Mater ; 4(5): 4105-4118, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-34056563

RESUMO

Existing fluorescent labels used in life sciences are based on organic compounds with limited lifetime or on quantum dots which are either expensive or toxic and have low kinetic stability in biological environments. To address these challenges, luminescent nanomaterials have been conceived as hierarchical, core-shell structures with spherical morphology and highly controlled dimensions. These tailor-made nanophosphors incorporate Ln:YVO4 nanoparticles (Ln = Eu(III) and Er(III)) as 50 nm cores and display intense and narrow emission maxima centered at ∼565 nm. These cores can be encapsulated in silica shells with highly controlled dimensions as well as functionalized with chitosan or PEG5000 to reduce nonspecific interactions with biomolecules in living cells. Confocal fluorescence microscopy in living prostate cancer cells confirmed the potential of these platforms to overcome the disadvantages of commercial fluorophores and their feasibility as labels for multiplexing, biosensing, and imaging in life science assays.


Assuntos
Materiais Biocompatíveis/química , Corantes Fluorescentes/química , Imagem Óptica , Neoplasias da Próstata/diagnóstico por imagem , Linhagem Celular Tumoral , Humanos , Elementos da Série dos Lantanídeos/química , Masculino , Teste de Materiais , Nanopartículas/química , Tamanho da Partícula , Compostos de Vanádio/química , Ítrio/química
19.
Appl Opt ; 60(11): 3044-3048, 2021 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-33983198

RESUMO

Yttrium aluminum garnet (YAG) doped with Ce was synthesized via the co-precipitation method with NH4HCO3 as the precipitant. The spectroscopic properties and the effects of the Ce doping concentration and sintering atmosphere on the crystal phase were investigated. The dosimeter of YAG:Ce phosphor material was prepared to study the radioluminescence (RL) characteristics of a clinical linear accelerator. A satisfying linear relationship between the radiation dose and RL signal was obtained, which provided a reference for the YAG:Ce phosphor material used in radiotherapy and real-time remote radiation detection.


Assuntos
Alumínio/química , Cério/química , Corantes Fluorescentes/química , Ítrio/química , Relação Dose-Resposta à Radiação , Humanos , Radioterapia
20.
Mikrochim Acta ; 188(5): 147, 2021 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-33797618

RESUMO

Immunohistochemistry (IHC) and immunocytochemistry (ICC) are widely used to identify cancerous cells within tissues and cell cultures. Even though the optical microscopy evaluation is considered the gold standard, the limited range of useful labels and narrow multiplexing capabilities create an imminent need for alternative readout techniques. Laser-induced breakdown spectroscopy (LIBS) enables large-scale multi-elemental analysis of the surface of biological samples, e.g., thin section or cell pellet. It is, therefore, a potential alternative for IHC and ICC readout of various labels or tags (Tag-LIBS approach). Here, we introduce Tag-LIBS as a method for the specific determination of HER2 biomarker. The cell pellets were labeled with streptavidin-conjugated upconversion nanoparticles (UCNP) through a primary anti-HER2 antibody and a biotinylated secondary antibody. The LIBS scanning enabled detecting the characteristic elemental signature of yttrium as a principal constituent of UCNP, thus indirectly providing a reliable way to differentiate between HER2-positive BT-474 cells and HER2-negative MDA-MB-231 cells. The comparison of results with upconversion optical microscopy and luminescence intensity scanning confirmed that LIBS is a promising alternative for the IHC and ICC readout.


Assuntos
Biomarcadores Tumorais/análise , Nanopartículas/química , Receptor ErbB-2/análise , Anticorpos Imobilizados/imunologia , Biomarcadores Tumorais/imunologia , Linhagem Celular Tumoral , Estudos de Viabilidade , Fluoretos/química , Fluoretos/efeitos da radiação , Humanos , Imuno-Histoquímica/métodos , Luz , Nanopartículas/efeitos da radiação , Receptor ErbB-2/imunologia , Análise Espectral/métodos , Túlio/química , Túlio/efeitos da radiação , Ítrio/química , Ítrio/efeitos da radiação
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