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1.
Nanoscale ; 14(35): 12744-12756, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36000453

RESUMO

Using nanoparticles as carriers for drug delivery systems has become a widely applied strategy in therapeutics and diagnostics. However, the pattern of their intracellular distribution is yet to be clarified. Here we present an in vitro study on the incorporation of mesoporous silica nanoparticles conjugated with folate and loaded with a cytotoxic drug, Irinotecan. The nanoparticles count and distribution within the cell frame were evaluated by means of enhanced dark field microscopy combined with hyperspectral imagery and 3D reconstructions from double-labeled fluorescent samples. An original post-processing procedure was developed to emphasize the nanoparticles' localization in 3D reconstruction of cellular compartments. By these means, it has been shown that the conjugation of mesoporous silica nanoparticles with folate increases the efficiency of nanoparticles entering the cell and their preferential localization in the close vicinity of the nucleus. As revealed by metabolic viability assays, the nanoparticles functionalized with folate enhance the cytotoxic efficiency of Irinotecan.


Assuntos
Antineoplásicos , Nanopartículas , Portadores de Fármacos , Sistemas de Liberação de Medicamentos/métodos , Ácido Fólico , Células HeLa , Humanos , Irinotecano , Microscopia , Porosidade , Dióxido de Silício
2.
Sci Rep ; 10(1): 18062, 2020 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-33093462

RESUMO

The present study concerns the in vitro oxidative stress responses of non-malignant murine cells exposed to surfactant-tailored ZnO nanoparticles (NPs) with distinct morphologies and different levels of manganese doping. Two series of Mn-doped ZnO NPs were obtained by coprecipitation synthesis method, in the presence of either polyvinylpyrrolidone (PVP) or sodium hexametaphosphate (SHMTP). The samples were investigated by powder X-ray Diffraction, Transmission Electron Microscopy, Fourier-Transform Infrared and Electron Paramagnetic Resonance spectroscopic methods, and N2 adsorption-desorption analysis. The observed surfactant-dependent effects concerned: i) particle size and morphology; ii) Mn-doping level; iii) specific surface area and porosity. The relationship between the surfactant dependent characteristics of the Mn-doped ZnO NPs and their in vitro toxicity was assessed by studying the cell viability, intracellular reactive oxygen species (ROS) generation, and DNA fragmentation in NIH3T3 fibroblast cells. The results indicated a positive correlation between the specific surface area and the magnitude of the induced toxicological effects and suggested that Mn-doping exerted a protective effect on cells by diminishing the pro-oxidative action associated with the increase in the specific BET area. The obtained results support the possibility to modulate the in vitro toxicity of ZnO nanomaterials by surfactant-controlled Mn-doping.


Assuntos
Dano ao DNA/efeitos dos fármacos , Fibroblastos , Manganês , Espécies Reativas de Oxigênio/metabolismo , Tensoativos , Óxido de Zinco/farmacologia , Animais , Fragmentação do DNA/efeitos dos fármacos , Fibroblastos/metabolismo , Camundongos , Células NIH 3T3 , Nanopartículas , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Fosfatos/química , Povidona/química , Propriedades de Superfície , Óxido de Zinco/síntese química , Óxido de Zinco/toxicidade
3.
Int J Mol Sci ; 21(2)2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31936346

RESUMO

The aim of the manuscript is to discuss the influence of plant polyphenols in overcoming multidrug resistance in four types of solid cancers (breast, colorectal, lung and prostate cancer). Effective treatment requires the use of multiple toxic chemotherapeutic drugs with different properties and targets. However, a major cause of cancer treatment failure and metastasis is the development of multidrug resistance. Potential mechanisms of multidrug resistance include increase of drug efflux, drug inactivation, detoxification mechanisms, modification of drug target, inhibition of cell death, involvement of cancer stem cells, dysregulation of miRNAs activity, epigenetic variations, imbalance of DNA damage/repair processes, tumor heterogeneity, tumor microenvironment, epithelial to mesenchymal transition and modulation of reactive oxygen species. Taking into consideration that synthetic multidrug resistance agents have failed to demonstrate significant survival benefits in patients with different types of cancer, recent research have focused on beneficial effects of natural compounds. Several phenolic compounds (flavones, phenolcarboxylic acids, ellagitannins, stilbens, lignans, curcumin, etc.) act as chemopreventive agents due to their antioxidant capacity, inhibition of proliferation, survival, angiogenesis, and metastasis, modulation of immune and inflammatory responses or inactivation of pro-carcinogens. Moreover, preclinical and clinical studies revealed that these compounds prevent multidrug resistance in cancer by modulating different pathways. Additional research is needed regarding the role of phenolic compounds in the prevention of multidrug resistance in different types of cancer.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Flavonoides/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Flavonoides/efeitos adversos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia
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