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The design of polymeric biocompatible nanomaterials for biological and medical applications has received special attention in recent years. Among different polymers, the triblock type copolymers (EO)x(PO)y(EO)x or Pluronics® stand out due its favorable characteristics such as biocompatibility, low tissue adhesion, thermosensitivity, and structural capacity to produce different types of macro and nanostructures, e.g. micelles, vesicles, nanocapsules, nanospheres, and hydrogels. However, Pluronic itself is not the "magic bullet" and its functionalization via chemical synthesis following biologically oriented design rules is usually required aiming to improve its properties. Therefore, this paper presents some of the main publications on new methodologies for synthetic modifications and applications of Pluronic-based nanoconstructs in the biomedical field in the last 15 years. In general, the polymer modifications aim to improve physical-chemical properties related to the micellization process or physical entrapment of drug cargo, responsive stimuli, active targeting, thermosensitivity, gelling ability, and hydrogel formation. Among these applications, it can be highlighted the treatment of malignant neoplasms, infectious diseases, wound healing, cellular regeneration, and tissue engineering. Functionalized Pluronic has also been used for various purposes, including medical diagnosis, medical imaging, and even miniaturization, such as the creation of lab-on-a-chip devices. In this context, this review discusses the main scientific contributions to the designing, optimization, and improvement of covalently functionalized Pluronics aiming at new strategies focused on the multiple areas of the biomedical field.
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Nanoestructuras , Neoplasias , Humanos , Poloxámero/química , Polímeros/uso terapéutico , Micelas , Nanoestructuras/químicaRESUMEN
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 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 â¢O2- 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.
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Nanopartículas del Metal , Óxido de Zinc , Óxido de Zinc/química , Fotólisis , Nanopartículas del Metal/química , Plata/química , Luz , CatálisisRESUMEN
Silver nanoparticles (AgNPs) are incredibly versatile nanostructures that more recently have been exploited to create advanced optoelectronic materials due enhancement of local magnetic field after its irradiation. However, the use of AgNPs as nanoantennas to amplify photophysical properties of close photosensitizer (PS) molecules in photodynamic therapy is still underexplored. The reason for that is the difficulty to control crucial parameters such as silver-PS distance in aqueous solution. In this scenario, here we propose a nanohybrid system where AgNP/PS distance is controlled by a thin layer of different Pluronic copolymers. The controllable distance and aqueous stability of proposed nanohybrids allow a tunable enhancement of fluorescence emission and singlet oxygen generation of some selected PS molecules. A detailed mechanism investigation demonstrated that the observed metal-enhanced photophysics is due to magnetic field enhancement close to AgNP surface (AgNP/PS distance-controlled effect) and the resonant coupling of AgNP hot electrons and HOMO-LUMO energies of the PS (AgNP/PS spectral overlap-controlled effect). These results show that the rational design in engineering new nanohybrid structures allowed photophysical improvement of PS molecules in aqueous solution in a tunable way and point out Pluronic-based AgNP/PS nanohybrids as a smart material for further developments aiming at theranostic applications in photodynamic therapy.
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Nanopartículas del Metal , Plata , Nanopartículas del Metal/química , Fármacos Fotosensibilizantes , Poloxámero , Polímeros , Plata/químicaRESUMEN
Nanotechnology development provides new strategies to improve different treatment modalities by integration of multiple molecules in a single multifunctional nanoparticle. In this scenario, we highlight silver nanoparticles (AgNPs) favorable optical properties such as absorption and emission of light in the visible region of the spectrum. This allows its synergic combination with the photosensitizer molecule methylene blue (MB) in order to improve outcomes in photodynamic-based therapies. Therefore, we engineered here a new multifunctional nanostructured system based in the synthesis of pluronic-based AgNP/MB nanohybrids inspired by the concept of supramolecular chemistry. Silver reduction in water and Pluronic F127 aqueous solutions in the presence of hydrogen peroxide as etching agent at several concentrations induced the formation of anisotropic forms of AgNPs. Electronic absorption and TEM studies demonstrated a greater kinetic and morphological control for Pluronic synthetized NPs. The smart design of the proposed nanohybrids favored the enhancement of MB photophysical properties such as fluorescence emission and singlet oxygen production due a synergic action from resonant coupling between AgNP magnetic field and MB molecules. Results also demonstrated that AgNP-MB distance modulation in Pluronic matrix is a relevant parameter in MB photophysical improvement. Finally, since AgNP absorbance spectrum is dependent on AgNP shape, it plays a critical role in the improvement of MB photophysical properties. These results show that the rational design in engineering new multifunctional nanoparticles is essential and point out that Pluronic AgNP/MB nanohybrids as a smart material for further developments aiming photodynamic-based therapies.
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Nanopartículas del Metal , Fotoquimioterapia , Azul de Metileno , Poloxámero , PlataRESUMEN
The high incidence of cancer, necessity of treatment, and prognosis times are urgent issues that need to be addressed. In this work, we present DPPC liposomes coated with F127 triblock copolymers as a promising alternative in drug delivery systems for cancer therapy. The proposed mixed liposomes exhibit adequate size, high stability, and passive targeting that result from the EPR effect. An interesting strategy to obtain both passive and active targeting is the vectorization with a covalent bond between F127 and Biotin (a vitamin). Cancer cells can overexpress Biotin receptors, such as Avidin. Here, we evaluate the cytotoxic effects of the erythrosine-decyl ester (ERYDEC). This is a photosensitizer that can be utilized in photodynamic therapy (PDT) and incorporated in DPPC liposomes coated with F127 (F127/DPPC) and the biotinylated-F127 (F127-B/DPPC). The results showed that DPPC liposomes were efficiently mixed with common F127 or F127B, exhibiting adequate physical properties with simple and low-cost preparation. An HABA/Avidin assay showed the amount of Biotin available at the liposome surface. In addition, ERYDEC interaction with lipid vesicles showed high encapsulating efficiency and slow release kinetics. The ERYDEC monomeric species are represented by high light absorption and high singlet oxygen generation (1O2), which confirm the presence of the drug in its monomeric state, as required for PDT. The ERYDEC/liposome system showed high stability and absence of significant cytotoxic effects (absence of light) in fibroblasts of the Mus musculus cell line. In addition, phototoxicity studies showed that ERYDEC/liposomes were able to inhibit cancer cells. However, in the biotinylated system, the effect was much greater than the common F127 coating. This dramatically decreased the inhibitory concentration of CC50 and CC90. In addition, cellular uptake studies based on fluorescence properties of ERYDEC showed that a two-hour incubation period was enough for the uptake by the cell. Therefore, the new vectorized-coated liposome is a potential system for use in cancer treatments, considering that it is a theranostic platform.
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Biotina/química , Liberación de Fármacos , Fármacos Fotosensibilizantes/farmacología , Animales , Biotinilación , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Eritrosina/farmacología , Humanos , Hidrodinámica , Liposomas , Tamaño de la Partícula , Fotoquimioterapia , Fármacos Fotosensibilizantes/química , Poloxámero/química , Espectrofotometría UltravioletaRESUMEN
Introduction: 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. Areas covered: 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. Expert opinion: Despite the efforts of different companies and research groups, several drawbacks, such as the lack of relevant in vivo 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.
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Antineoplásicos/administración & dosificación , Neoplasias/tratamiento farmacológico , Profármacos/administración & dosificación , Animales , Antineoplásicos/farmacocinética , Antineoplásicos/farmacología , Desarrollo de Medicamentos , Humanos , Inmunoconjugados/administración & dosificación , Inmunoconjugados/farmacocinética , Inmunoconjugados/farmacología , Terapia Molecular Dirigida , Nanotecnología , Neoplasias/patologíaRESUMEN
In this paper, we introduce a new drug delivery system (DDS) called magneto low-density nanoemulsion (MLDE), which can carry maghemite nanoparticles and Chlorin e6 as an active photosensitizer drug. This design can enhance tumor damage after minor heat dissipation and/or minimum visible light photosensitization doses by classical magnetic hyperthermia (MHT) and photodynamic therapy (PDT), respectively. We establish protocols to prepare the MLDE and to load the drug combination onto it. The MLDE prepared herein is nanometric (<200â¯nm), has high encapsulation efficiency, and is stable for at least 12â¯months in water dispersions. Flow cytometry results demonstrated that MLDE presents targeted selectivity toward the MCF-7 breast cancer cell line but not in NHI-3T3 mouse fibroblast cell lines, because the MCF-7 cancer cell surface contains overexpressed low density lipoprotein (LDL) receptors. Despite this targeted effect, MHT or PDT alone does not prompt significant antiproliferative outcomes. On the other hand, MHT and PDT in combination induce a strong and synergic action on MCF-7 cells and reduce the cell viability. In conclusion, the developed MLDE deserves further investigation because it is biocompatible, displays good encapsulation efficiency, and is highly stable. Moreover, it is selectively taken up by cancer cell surfaces with receptor recognition based on LDL receptor overexpression, which potentiates the action of combined MHT and PDT.
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Magnetismo , Nanoestructuras/química , Animales , Supervivencia Celular/efectos de los fármacos , Clorofilidas , Portadores de Fármacos/química , Humanos , Hipertermia Inducida , Luz , Células MCF-7 , Ratones , Células 3T3 NIH , Neoplasias/tratamiento farmacológico , Tamaño de la Partícula , Fotoquimioterapia , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Porfirinas/química , Porfirinas/farmacología , Porfirinas/uso terapéuticoRESUMEN
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 24â¯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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Budesonida/administración & dosificación , Sistemas de Liberación de Medicamentos , Pulmón/metabolismo , Poloxámero/química , Administración por Inhalación , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/química , Antiinflamatorios/farmacocinética , Budesonida/química , Budesonida/farmacocinética , Modelos Animales de Enfermedad , Portadores de Fármacos/química , Interacciones Hidrofóbicas e Hidrofílicas , Lipopolisacáridos/toxicidad , Masculino , Micelas , Nebulizadores y Vaporizadores , Tamaño de la Partícula , Neumonía/tratamiento farmacológico , Ratas , Ratas Wistar , Factores de Tiempo , Distribución TisularRESUMEN
Selection of an efficient light source is fundamental in the development of photodynamic therapy (PDT) protocols. However, few studies provide a comparison of different light sources with regard to phototoxic effects. Here, we compared the cell death induced by photoactivation of chloro-aluminiumphtalocyanine (AlClPc)-loaded human serum albumin nanoparticles under irradiation with different light sources: continuous laser (CL), pulsed laser (PL), and light-emitting diode (LED). Cells were exposed to three different AlClPc concentrations (1, 3, and 5µM) and three different light doses (200, 500, and 700mJ/cm2) for each light source. Cell death and differentiation of apoptosis and necrosis pathway were measured by flow cytometry. CL was the best light source for improving the photodynamic action of AlClPc-loaded albumin nanoparticles in glioblastoma cells and avoiding undesirable side effects, especially at low photosensitizer doses (200mJ/cm2). In addition, apoptosis was the main cell death pathway in all evaluated cases (70% for CL, and greater than 50% for PL and LED). In conclusion, the search for optimal light sources and light/photosensitizer doses is a crucial step in improving PDT outcomes and enhancing the clinical translation of PDT.
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Glioblastoma/tratamiento farmacológico , Indoles/farmacología , Compuestos Organometálicos/farmacología , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Albúminas/química , Apoptosis/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Citometría de Flujo , Humanos , Indoles/administración & dosificación , Nanopartículas/química , Compuestos Organometálicos/administración & dosificación , Fotoquimioterapia/instrumentación , Fármacos Fotosensibilizantes/administración & dosificaciónRESUMEN
INTRODUCTION: Nanomedicine development allowed the discovery of new photosensitizers (PS) and drug delivery systems (DDS) to overcome current issues on phototherapy. Nano-engineered materials have the potential to improve the solubility of PS, control drug pharmacokinetics, decreasing side effects, increasing bioavailability, and overcoming multidrug resistance. A recent approach is the co-delivery of PS with other therapeutic agents in a multimodal platform for synergic and improved results. Areas covered: This paper discusses the delivery of PS-nanostructured platforms for conventional, photothermal, and antimicrobial photodynamic therapies, as well as in a recent therapeutic modality for photobiomodulation, covering applications of cancer diagnosis, targeting to skin pathogens, photoregeneration and wound healing. The focus of the present review is to describe the use of different DDS to enhance the therapeutic outcomes triggered by the combination of delivered PS, light, and oxygen. Expert opinion: Nanotechnology allowed the development of site-specific delivery of PS molecules, expanding possibilities poorly explored before to enhance photodynamic efficacy and extrapolate the concept to other treatment protocols. Research in this area embraces potential and pitfalls of PS delivery, allowing new clinical phase outcomes and long-term issues to be established, which will impact on several biomedical applications.
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Sistemas de Liberación de Medicamentos/métodos , Nanoestructuras/química , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/administración & dosificación , Resistencia a Medicamentos , Quimioterapia Combinada , Humanos , Fármacos Fotosensibilizantes/farmacocinéticaRESUMEN
Nanotechnology development provides new strategies to treat cancer by integration of different treatment modalities in a single multifunctional nanoparticle. In this scenario, we applied the multifunctional Pluronic P123/F127 mixed micelles for Verteporfin-mediated photodynamic therapy in PC3 and MCF-7 cancer cells. Micelles functionalization aimed the targeted delivery by the insertion of biotin moiety on micelle surface and fluorescence image-based through rhodamine-B dye conjugation in the polymer chains. Multifunctional Pluronics formed spherical nanoparticulated micelles that efficiently encapsulated the photosensitizer Verteporfin maintaining its favorable photophysical properties. Lyophilized formulations were stable at least for 6months and readily reconstituted in aqueous media. The multifunctional micelles were stable in protein-rich media due to the dual Pluronic mixed micelles characteristic: high drug loading capacity provided by its micellar core and high kinetic stability due its biocompatible shell. Biotin surface functionalized micelles showed higher internalization rates due biotin-mediated endocytosis, as demonstrated by competitive cellular uptake studies. Rhodamine B-tagged micelles allowed monitoring cellular uptake and intracellular distribution of the formulations. Confocal microscopy studies demonstrated a larger intracellular distribution of the formulation and photosensitizer, which could drive Verteporfin to act on multiple cell sites. Formulations were not toxic in the dark condition, but showed high Verteporfin-induced phototoxicity against both cancer cell lines at low drug and light doses. These results point Verteporfin-loaded multifunctional micelles as a promising tool to further developments in photodynamic therapy of cancer.
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Portadores de Fármacos , Micelas , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Fotoquimioterapia , Poloxaleno , Poloxámero , Porfirinas , Nanomedicina Teranóstica/métodos , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacología , Femenino , Humanos , Células MCF-7 , Masculino , Neoplasias/metabolismo , Neoplasias/patología , Poloxaleno/química , Poloxaleno/farmacocinética , Poloxaleno/farmacología , Poloxámero/química , Poloxámero/farmacocinética , Poloxámero/farmacología , Porfirinas/química , Porfirinas/farmacocinética , Porfirinas/farmacología , VerteporfinaRESUMEN
It was evaluated the properties of the xanthene dyes Erythrosin B, Eosin Y and theirs Methyl, Butyl and Decyl ester derivatives as possible photosensitizers (PS) for photodynamic treatments. The more hydrophobic dyes self-aggregate in water/ethanol solutions above 70% water (vol/vol) in the mixture. In buffered water, these PS were encapsulated in Pluronic polymeric surfactants of P-123 and F-127 by two methodologies: direct addition and the thin-film solid dispersion methods. The thin-film solid method provided formulations with higher stabilities besides effective encapsulation of the PS as monomers. Size measurements demonstrated that Pluronic forms self-assembled micelles with uniform size, which present slightly negative surface potential and a spherical form detected by TEM microscopy. The ester length modulates xanthene localization in the micelle, which is deeper with the increase in the alkyl chain. Moreover, some PS are distributed into two populations: one on the corona micelle interface shell (PEO layer) and the other into the core (PPO region). Although all PS formulations show high singlet oxygen quantum yield, promising results were obtained for Erythrosin B esters with the hydrophobic P-123, which ensures their potential as drug for clinical photodynamic applications.
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Colorantes , Micelas , Nanoestructuras/química , Fármacos Fotosensibilizantes , Polímeros/química , Xantenos/química , Colorantes/química , Colorantes/farmacología , Estabilidad de Medicamentos , Etanol/química , Microscopía Electrónica de Transmisión , Fotoquimioterapia , Fármacos Fotosensibilizantes/química , Poloxámero/análogos & derivados , Poloxámero/química , Agua/químicaRESUMEN
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.
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BACKGROUND: Photodynamic inactivation of microorganisms is based on a photosensitizing substance which, in the presence of light and molecular oxygen, produces singlet oxygen, a toxic agent to microorganisms and tumor cells. This study aimed to evaluate singlet oxygen quantum yield of erythrosine solutions illuminated with a halogen light source in comparison to a LED array (control), and the photodynamic effect of erythrosine dye in association with the halogen light source on Streptococcus mutans. METHODS: Singlet oxygen quantum yield of erythrosine solutions was quantified using uric acid as a chemical-probe in an aqueous solution. The in vitro effect of the photodynamic antimicrobial activity of erythrosine in association with the halogen photopolimerizing light on Streptococcus mutans (UA 159) was assessed during one minute. Bacterial cultures treated with erythrosine alone served as negative control. RESULTS: Singlet oxygen with 24% and 2.8% degradation of uric acid in one minute and a quantum yield of 0.59 and 0.63 was obtained for the erythrosine samples illuminated with the halogen light and the LED array, respectively. The bacterial cultures with erythrosine illuminated with the halogen light presented a decreased number of CFU mL(-1) in comparison with the negative control, with minimal inhibitory concentrations between 0.312 and 0.156mgmL(-1). CONCLUSIONS: The photodynamic response of erythrosine induced by the halogen light was capable of killing S. mutans. Clinical trials should be conducted to better ascertain the use of erythrosine in association with halogen light source for the treatment of dental caries.
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Luces de Curación Dental , Eritrosina/administración & dosificación , Iluminación/instrumentación , Fotoquimioterapia/instrumentación , Oxígeno Singlete/administración & dosificación , Streptococcus mutans/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Desinfección/instrumentación , Desinfección/métodos , Relación Dosis-Respuesta a Droga , Relación Dosis-Respuesta en la Radiación , Quimioterapia Combinada/métodos , Humanos , Luz , Iluminación/métodos , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/administración & dosificación , Oxígeno Singlete/efectos de la radiación , Streptococcus mutans/citología , Streptococcus mutans/fisiología , Resultado del TratamientoRESUMEN
With the aim to develop alternative therapeutic tools for the treatment of resistant cancers, here we propose targeted Pluronic(®) P123/F127 mixed micelles (PMM) delivering niclosamide (NCL) as a repositioning strategy to treat multidrug resistant non-small lung cancer cell lines. To build multifunctional PMM for targeting and imaging, Pluronic(®) F127 was conjugated with biotin, while Pluronic(®) P123 was fluorescently tagged with rhodamine B, in both cases at one of the two hydroxyl end groups. This design intended to avoid any interference of rhodamine B on biotin exposition on PMM surface, which is a key fundamental for cell trafficking studies. Biotin-decorated PMM were internalized more efficiently than non-targeted PMM in A549 lung cancer cells, while very low internalization was found in NHI3T3 normal fibroblasts. Biotin-decorated PMM entrapped NCL with good efficiency, displayed sustained drug release in protein-rich media and improved cytotoxicity in A549 cells as compared to free NCL (P<0.01). To go in depth into the actual therapeutic potential of NCL-loaded PMM, a cisplatin-resistant A549 lung cancer cell line (CPr-A549) was developed and its multidrug resistance tested against common chemotherapeutics. Free NCL was able to overcome chemoresistance showing cytotoxic effects in this cell line ascribable to nucleolar stress, which was associated to a significant increase of the ribosomal protein rpL3 and consequent up-regulation of p21. It is noteworthy that biotin-decorated PMM carrying NCL at low doses demonstrated a significantly higher cytotoxicity than free NCL in CPr-A549. These results point at NCL-based regimen with targeted PMM as a possible second-line chemotherapy for lung cancer showing cisplatin or multidrug resistance.
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Biotina/administración & dosificación , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias Pulmonares , Niclosamida/administración & dosificación , Poloxaleno/administración & dosificación , Poloxámero/administración & dosificación , Células A549 , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/metabolismo , Biotina/metabolismo , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Relación Dosis-Respuesta a Droga , Sistemas de Liberación de Medicamentos/métodos , Resistencia a Antineoplásicos/fisiología , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Ratones , Micelas , Células 3T3 NIH , Niclosamida/metabolismo , Poloxaleno/metabolismo , Poloxámero/metabolismo , Proteína Ribosomal L3RESUMEN
In chemotherapy a fine balance between therapeutic and toxic effects needs to be found for each patient, adapting standard combination protocols each time. Nanotherapeutics has been introduced into clinical practice for treating tumors with the aim of improving the therapeutic outcome of conventional therapies and of alleviating their toxicity and overcoming multidrug resistance. Photodynamic therapy (PDT) is a clinically approved, minimally invasive procedure emerging in cancer treatment. It involves the administration of a photosensitizer (PS) which, under light irradiation and in the presence of molecular oxygen, produces cytotoxic species. Unfortunately, most PSs lack specificity for tumor cells and are poorly soluble in aqueous media, where they can form aggregates with low photoactivity. Nanotechnological approaches in PDT (nanoPDT) can offer a valid option to deliver PSs in the body and to solve at least some of these issues. Currently, polymeric nanoparticles (NPs) are emerging as nanoPDT system because their features (size, surface properties, and release rate) can be readily manipulated by selecting appropriate materials in a vast range of possible candidates commercially available and by synthesizing novel tailor-made materials. Delivery of PSs through NPs offers a great opportunity to overcome PDT drawbacks based on the concept that a nanocarrier can drive therapeutic concentrations of PS to the tumor cells without generating any harmful effect in non-target tissues. Furthermore, carriers for nanoPDT can surmount solubility issues and the tendency of PS to aggregate, which can severely affect photophysical, chemical, and biological properties. Finally, multimodal NPs carrying different drugs/bioactive species with complementary mechanisms of cancer cell killing and incorporating an imaging agent can be developed. In the following, we describe the principles of PDT use in cancer and the pillars of rational design of nanoPDT carriers dictated by tumor and PS features. Then we illustrate the main nanoPDT systems demonstrating potential in preclinical models together with emerging concepts for their advanced design.
Asunto(s)
Nanopartículas , Neoplasias/terapia , Fotoquimioterapia , Polímeros/química , HumanosRESUMEN
Strong light absorption and high levels of singlet oxygen production indicate erythrosin B as a viable candidate as a photosensitizer in photodynamic therapy or photodynamic inactivation of microorganisms. Under light irradiation, erythrosin B undergoes a photobleaching process that can decrease the production of singlet oxygen. In this paper, we use thermal lens spectroscopy to investigate photobleaching in micellar solutions of erythrosin ester derivatives: methyl, butyl, and decyl esters in low concentrations of non-ionic micellar aqueous solutions. Using a previously developed thermal lens model, it was possible to determine the photobleaching rate and fluorescence quantum efficiency for dye-micelle solutions. The results suggest that photobleaching is related to the intensity of the dye-micelle interaction and demonstrate that the thermal lens technique can be used as a sensitive tool for quantitative measurement of photochemical properties in very diluted solutions.
Asunto(s)
Eritrosina/química , Colorantes Fluorescentes/química , Fármacos Fotosensibilizantes/química , Ésteres/química , Micelas , Fotoblanqueo , Fotólisis , Agua/químicaRESUMEN
A ß-cyclodextrin nanosponge cross-linked with pyromellitic dianhydride (ßNS-PYRO) is reported for the first time as multifunctional ingredient in semisolid formulations for drug delivery to the skin. The role of ßNS-PYRO on solubilization and stabilization of the photosensitizer benzoporphyrin-derivative monoacid ring A (BPDMA) and all-trans retinoic acid (atRA) as well as its effect on skin permeation of diclofenac (DIC) was investigated. Aqueous solutions, gels, and cream-gels were prepared from mixtures of ßNS-PYRO with a conventional gelling agent at specific ratios. The incorporation of BPDMA in ßNS-PYRO water solutions prevented its aggregation and gave kinetically stable complexes with high photostability and singlet oxygen generation upon irradiation. atRA incorporated in the ßNS-PYRO-containing gel demonstrated a remarkable stability as compared with the formulation without ßNS-PYRO, resulting in an eightfold increase of its lifetime. Skin permeation studies highlighted that ßNS-PYRO in gels and cream-gels containing DIC significantly decreased the amount of drug permeated through the skin while increasing its amount in stratum corneum and viable epidermis. Overall, swellable ßNS-PYRO turns to be a multifunctional coingredient with potential in topical monophasic and biphasic formulations to stabilize light-sensitive drugs and to localize the action of highly penetrating drugs in the external layers of skin.
Asunto(s)
Nanoestructuras/administración & dosificación , Nanoestructuras/química , Piel/metabolismo , Agua/química , beta-Ciclodextrinas/administración & dosificación , beta-Ciclodextrinas/química , Animales , Química Farmacéutica/métodos , Geles/administración & dosificación , Geles/química , Permeabilidad , Absorción Cutánea , PorcinosRESUMEN
Xanthenes form to an important class of dyes which are widely used. Most of them present three acid-base groups: two phenolic sites and one carboxylic site. Therefore, the pKa determination and the attribution of each group to the corresponding pKa value is a very important feature. Attempts to obtain reliable pKa through the potentiometry titration and the electronic absorption spectrophotometry using the first and second orders derivative failed. Due to the close pKa values allied to strong UV-Vis spectral overlap, multivariate analysis, a powerful chemometric method, is applied in this work. The determination was performed for eosin Y, erythrosin B, and bengal rose B, and also for other synthesized derivatives such as 2-(3,6-dihydroxy-9-acridinyl) benzoic acid, 2,4,5,7-tetranitrofluorescein, eosin methyl ester, and erythrosin methyl ester in water. These last two compounds (esters) permitted to attribute the pKa of the phenolic group, which is not easily recognizable for some investigated dyes. Besides the pKa determination, the chemometry allowed for estimating the electronic spectrum of some prevalent protolytic species and the substituents effects evaluation.