Despite advances in cancer therapies, glioblastoma multiforme treatment remains inefficient due to the brain-blood barrier (BBB) inhibitory activity and to the low temozolomide (TMZ) chemotherapeutic ...selectivity. To improve therapeutic outcomes, in this work we propose two strategies, (i) photodynamic therapy (PDT) as adjuvant treatment and (ii) engineering of multifunctional theranostic/targeted nanoparticles ( m-NPs) that integrate biotin as a targeting moiety with rhodamine-B as a theranostic agent in pluronic P85/F127 copolymers. These smart m-NPs can surmount the BBB and coencapsulate multiple cargoes under optimized conditions. Overall, the present study conducts a rational m-NP design, characterization, and optimizes the formulation conditions. Confocal microscopy studies on T98-G, U87-MG, and U343 glioblastoma cells and on NIH-3T3 normal fibroblast cells show that the m-NPs and the encapsulated drugs are selectively taken up by tumor cells presenting a broad intracellular distribution. The formulations display no toxicity in the absence of light and are not toxic to healthy cells, but they exert a robust synergic action in cancer cells in the case of concomitant PDT/TMZ treatment, especially at low TMZ concentrations and higher light doses, as demonstrated by nonlinear dose-effect curves based on the Chou-Talalay method. The results evidenced different mechanisms of action related to the disjoint cell cycle phases at the optimal PDT/TMZ ratio. This effect favors synergism between the PDT and the chemotherapy with TMZ, enhances the antiproliferative effect, and overcomes cross-resistance mechanisms. These results point out that m-NP-based PDT adjuvant therapy is a promising strategy to improve TMZ-based glioblastoma multiforme treatments.
The use of copper as an antimicrobial agent has a long history and has gained renewed interest in the context of the COVID-19 pandemic. In this study, the authors investigated the antimicrobial ...properties of an alloy composed of copper with a small percentage of silver (Cu-0.03% wt.Ag). The alloy was tested against various pathogens, including
,
,
,
, and the H1N1 virus, using contact exposure tests. Results showed that the alloy was capable of inactivating these pathogens in two hours or less, indicating its strong antimicrobial activity. Electrochemical measurements were also performed, revealing that the small addition of silver to copper promoted a higher resistance to corrosion and shifted the formation of copper ions to higher potentials. This shift led to a slow but continuous release of Cu
ions, which have high biocidal activity. These findings show that the addition of small amounts of silver to copper can enhance its biocidal properties and improve its effectiveness as an antimicrobial material.
The development of drugs for photodynamic therapy (PDT) is an important area of research due to their growing use in medical applications. Therefore, it is important to develop new bioassay methods ...for PDT photosensitizers that are inexpensive, easy to handle and highly sensitive to environmental conditions. Xanthene dyes (fluorescein, rose bengal B, erythrosine B and eosin Y) with LED light sources were investigated using Artemia salina as a bioindicator of photodynamic activity. In this study, three factors were investigated: (i) photosensitizers concentration, (ii) the LED irradiation time and (iii) the waiting time between the addition of the photosensitizers and the beginning of the irradiation. To analyze the photo-killing of A. salina, it was employed a 2³ full factorial design. The death of A. salina was related to dye structure and the interaction between the irradiation time and the photosensitizers concentration. About 60% of crustaceans death was obtained using rose bengal B, which presentes the highest quantum yield of singlet oxygen due to the number of iodide substituents in the xanthenes ring. The proposed bioassay using A. salina, xanthene dyes and LED irradiation was found suitable for quantitative PDT drug evaluation.
However, the process of cleaning the material using acid pickling generates hazardous metal-rich acid residue that is harmful to the environment and expensive to dispose of. Therefore, this study ...aimed to recover the acid pickling residue from the Cu0.69Zn0.26Ni0.05 alloy. By using an economically viable and surfactant-free one-pot coprecipitation hydrothermal process, a ZnO-rich microcomposite material was obtained, which had a high recovery yield of 20 g/L by reusing residual water in a cyclic process. The material's composition was confirmed through electronic and crystalline characterizations determined by UV-Vis, Photoluminescence, FTIR, XRD, and XPS. Moreover, the morphological characterization showed that the wurtzite ZnO grows on the CuO surface, forming rod-like structures with high surface areas, as observed through SEM and TEM analysis. The microstructure exhibits favorable properties that enable the degradation of a pollutant model in an aqueous solution, as well as the inactivation of multidrug-resistant bacteria. Unlike other works in the literature, the creation of a valuable product from a harmful residue did not require complex metal separation steps. These promising results bode well for the development of functional materials based on green economy principles, thereby facilitating large-scale treatment of industrial metallurgy residues.
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•Recovering metal from a realistic metallurgic acid-pickling wastewater.•One-pot coprecipitation methodology allowed a high recovery yield of 20 g/L.•Wurtzite ZnO grows as rods on the CuO surface, forming high surface areas.•Composite material presents favorable photocatalytic and antibacterial properties.•Circular economy concepts applicable to large-scale metallurgy.
The correct selection of a dye that has effective action as a photosensitizer is a primary concern for successful therapeutic outcomes. The effectiveness of the photodynamic agent is related to both ...the targeting of cell membranes and the photochemical yield of the chosen dye. The distributions of xanthene derivatives Eosin Y, Erythrosin B, and Rose Bengal B in vesicles of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) in both liquid-crystalline and gel phases were investigated by fluorescence spectroscopy. Binding constants, fluorescence anisotropy, fluorescence quenching, fluorescence quantum yield, and fluorescence resonance energy transfer at physiological pH conditions were determined. To Erythrosin B and Eosin Y, the iodide quenching rate constant was shown to involve a sphere of action mechanism driven by a specific interaction between Erythrosin B and Eosin Y molecules and the choline head-group of the phospholipid; in contrast, Rose Bengal B was located deep in the membrane and this mechanism was not present. The dyes can be ordered by their penetration depth in the membrane, and this order was found to be Eosin Y < Erythrosin B < Rose Bengal B. These results demonstrate a rational approach for the screening of more active agents for photodynamic therapy based on the affinity between the xanthene derivatives and DPPC vesicles.
Here, we developed Pluronic
P123/F127 (poloxamer) mixed micelles for the intravenous delivery of the anticancer drug sorafenib (SRB) or its combination with verteporfin (VP), a photosensitizer for ...photodynamic therapy that should complement well the cytotoxicity profile of the chemotherapeutic. SRB loading inside the core of micelles was governed by the drug:poloxamer weight ratio, while in the case of the SRB-VP combination, a mutual interference between the two drugs occurred and only specific ratios could ensure maximum loading efficiency. Coentrapment of SRB did not alter the photophysical properties of VP, confirming that SRB did not participate in any bimolecular process with the photosensitizer. Fluorescence resonance energy-transfer measurement of micelles in serum protein-containing cell-culture medium demonstrated the excellent stability of the system in physiologically relevant conditions. These results were in line with the results of the release study showing a release rate of both drugs in the presence of proteins slower than in phosphate buffer. SRB release was sustained, while VP remained substantially entrapped in the micelle core. Cytotoxicity studies in MDA-MB231 cells revealed that at 24 hours, SRB-loaded micelles were more active than free SRB only at very low SRB concentrations, while at 24+24 hours a prolonged cytotoxic effect of SRB-loaded micelles was observed, very likely mediated by the block in the S phase of the cell cycle. The combination of SRB with VP under light exposure was less cytotoxic than both the free combination and VP-loaded micelles + SRB-loaded micelles combination. This behavior was clearly explainable in terms of micelle uptake and intracellular localization. Besides the clear advantage of delivering SRB in poloxamer micelles, our results provide a clear example that each photochemotherapeutic combination needs detailed investigations on their particular interaction, and no generalization on enhanced cytotoxic effects should be derived a priori.
In this work, we propose zinc oxide (ZnO) surface functionalization with plasmonic silver nanoparticles (AgNP) of different sizes and shapes (spheres, prisms, and rods) creating ZnO/AgNP nanohybrids. ...These were characterized by UV-Vis spectroscopy, X-ray diffraction, transmission electron microscopy, Fourier-transform infrared spectroscopy, diffuse reflectance spectroscopy, and photoluminescence spectroscopy. Surface functionalization with AgNP improved photocatalyst electronic properties, its visible light absorption, and slow electron/hole recombination on the ZnO surface. Photocatalysis assays performed with a polychromatic Hg lamp degraded methyl orange, a model of persistent organic pollutant in water. A systematic study showed that the photodegradation kinetics of the nanohybrids are significantly more efficient than pure ZnO (up to 18 times) and that AgNP size and especially its shape are important in dye degradation. Mechanistic studies revealed that degradation occurred by direct dye reduction on the ZnO surface holes, ZnO electron transfer to Ag followed by •O
2
−
formation, and direct injection of AgNP hot electrons in the ZnO conduction band. The last effect was stronger for anisotropic AgNP, which explains their high kinetic degradation rates. Therefore, the rational design in ZnO/AgNP nanohybrid engineering and a systematic approach used in this manuscript allowed a detailed description of photodegradation process that occur at ZnO/AgNP interface. Our results are not conclusive about AgNP size; on the other hand, it clearly demonstrates that anisotropic nanoparticles (as Ag rods and prims) present superior photodegradation efficiency and are promising particles for further large-scale use of solar-irradiated nanohybrids.
Prodrugs for targeted cancer therapy Souza, Carla; Pellosi, Diogo Silva; Tedesco, Antonio Claudio
Expert review of anticancer therapy,
06/2019, Letnik:
19, Številka:
6
Journal Article
Recenzirano
: Prodrugs have been used to improve the selectivity and efficacy of cancer therapy by targeting unique abnormal markers that are overexpressed by cancer cells and are absent in normal tissues. In ...this context, different strategies have been exploited and new ones are being developed each year.
: In this review, an integrated view of the potential use of prodrugs in targeted cancer therapy is provided. Passive and active strategies are discussed in light of the advantages of each one and some successful examples are provided, as well as the clinical status of several prodrugs. Among them, antibody-drug conjugates (ADCs) are the most commonly used. However, several drawbacks, including limited prodrug uptake, poor pharmacokinetics, immunogenicity problems, difficulties in selective targeting and gene expression, and optimized bystander effects limit their clinical applications.
: Despite the efforts of different companies and research groups, several drawbacks, such as the lack of relevant
models, complexity of the human metabolism, and economic limitations, have hampered the development of new prodrugs for targeted cancer therapy. As a result, we believe that the combination of prodrugs with cancer nanotechnology and other newly developed approaches, such as aptamer-conjugated nanomaterials, are efficient strategies.
The use of conjugated polymers (CPs) and metallic nanoparticles is an interesting way to form nanocomposites with improved optical properties. For instance, a nanocomposite with high sensitivity can ...be produced. However, the hydrophobicity of CPs may hamper applications due to their low bioavailability and low operability in aqueous media. This problem can be overcome by forming thin solid films from an aqueous dispersion containing small CP nanoparticles. So, in this work we developed the formation of thin films of poly(9,9-dioctylfluorene-co-3,4-ethylenedioxythiophene) (PDOF-co-PEDOT) from its natural and nano form (NCP) from aqueous solution. These copolymers were then blended in films with triangular and spherical silver nanoparticles (AgNP) for future applicability as a SERS sensor of pesticides. TEM characterization showed that the AgNP were adsorbed on the NCP surface, forming a nanostructure with an average diameter of 90 nm (value according to that obtained by DLS) and with a negative potential zeta. These nanostructures were transferred to a solid substrate, forming thin and homogeneous films with different morphology of PDOF-co-PEDOT films, as observed by atomic force microscopy (AFM). XPS data demonstrated the presence of the AgNP in the thin films, as well as evidence that films with NCP are more resistant to the photo-oxidation process. Raman spectra showed characteristic peaks of the copolymer in the films prepared with NCP. It should also be noted the enhancement effect of Raman bands observed on films containing AgNP, a strong indication of the SERS effect induced by the metallic nanoparticles. Furthermore, the different geometry of the AgNP influences the way in which the adsorption between the NCP and the metal surface occurs, with a perpendicular adsorption between the NCP chains and the surface of the triangular AgNP.
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In this paper, we shed light on the potential of Pluronic® mixed micelles in lung delivery of poorly water-soluble drugs. To this purpose, Pluronic® P123/F127 mixed micelles (PMM), ...exhibiting superior stability in biological fluids, were loaded with budesonide (BUD), a model hydrophobic corticosteroid, and fully investigated focusing on their stability in pulmonary-relevant media, transport through the mucus barrier and aerodynamic behaviour in vitro. Then, lung bio-distribution and efficacy were evaluated in vivo, after intra-tracheal administration in rats. PMM showed excellent stability in saline, mucin, artificial airway mucus and simulated interstitial lung fluid. Likely due to their small size coupled with the hydrophilic biofouling shell, PMM did not interact with mucin and consequently diffused through artificial mucus. BUD was loaded with high efficiency in PMM and released at sustained rate in artificial mucus. BUD-PMM dispersion in saline was efficiently delivered through a common jet nebulizer without aggregation. After intratracheal administration in rats, PMM labelled with Rhodamine B persisted in the lung up to 24 h, while serum levels rapidly dropped. Finally, the effects of BUD-PMM in a rat model of lung inflammation induced by intra-tracheal aerosolization of lipopolysaccharide (LPS) from E. coli were investigated. Of note, a single intra-tracheal aerosolization of BUD-PMM significantly reduced bronchoalveolar neutrophil infiltration and the expression of protein/enzymes derived from the arachidonic acid cascade induced by LPS, whereas a control BUD aqueous suspension showed a weaker effect. Overall, this study demonstrates that inhalable formulations of PMM can be considered as a platform for local delivery of hydrophobic drugs at lungs worth of further consideration.
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