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Treatment failure in breast cancers overexpressing human epidermal growth factor receptor 2 (HER2) is associated mainly to the upregulation of human epidermal growth factor receptor 3 (HER3) oncoprotein linked to chemoresitence. Therefore, to increase patient survival, here a multimodal theranostic nanoplatform targeting both HER2 and HER3 is developed. This consists of doxorubicin-loaded branched gold nanoshells functionalized with the near-infrared (NIR) fluorescent dye indocyanine green, a small interfering RNA (siRNA) against HER3, and the HER2-specific antibody Transtuzumab, able to provide a combined therapeutic outcome (chemo- and photothermal activities, RNA silencing, and immune response). In vitro assays in HER2+ /HER3+ SKBR-3 breast cancer cells have shown an effective silencing of HER3 by the released siRNA and an inhibition of HER2 oncoproteins provided by Trastuzumab, along with a decrease of the serine/threonine protein kinase Akt (p-AKT) typically associated with cell survival and proliferation, which helps to overcome doxorubicin chemoresistance. Conversely, adding the NIR light therapy, an increment in p-AKT concentration is observed, although HER2/HER3 inhibitions are maintained for 72 h. Finally, in vivo studies in a tumor-bearing mice model display a significant progressively decrease of the tumor volume after nanoparticle administration and subsequent NIR light irradiation, confirming the potential efficacy of the hybrid nanocarrier.
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Neoplasias da Mama , Nanoconchas , Humanos , Animais , Camundongos , Feminino , Neoplasias da Mama/metabolismo , Proteínas Proto-Oncogênicas c-akt , Ouro , Receptor ErbB-2/genética , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , RNA Interferente Pequeno , Linhagem Celular TumoralRESUMO
Metal nanoparticles (NPs), particularly gold nanorods (AuNRs), appear as excellent platforms not only to transport and deliver bioactive cargoes but also to provide additional therapeutic responses for diseased cells and tissues and/or to complement the action of the carried molecules. In this manner, here, we optimized a previous developed metal-based nanoplatform composed of an AuNR core surrounded by a polymeric shell constructed by means of the layer-by-layer approach, and in which very large amounts of the antineoplasic drug doxorubicin (DOXO) in a single loading step and targeting capability thanks to an outer hyaluronic acid layer were incorporated by means of an optimized fabrication process (PSS/DOXO/PLL/HA-coated AuNRs). The platform retained its nanometer size with a negative surface charge and was colloidally stable in a range of physiological conditions, in which only in some of them some particle clustering was noted with no precipitation. In addition, the dual stimuli-responsiveness of the designed nanoplatform to both endogenous proteases and external applied light stimuli allows to perfectly manipulate the chemodrug release rates and profiles to achieve suitable pharmacodynamics. It was observed that the inherent active targeting abilities of the nanoplatfom allow the achievement of specific cell toxicity in tumoral cervical HeLa cells, whilst healthy ones such as 3T3-Balb fibroblast remain safe and alive in agreement with the detected levels of internalization in each cell line. In addition, the bimodal action of simultaneous chemo- and photothermal bioactivity provided by the platform largely enhances the therapeutic outcomes. Finally, it was observed that our PSS/DOXO/PLL/HA-coated AuNRs induced cell mortality mainly through apoptosis in HeLa cells even in the presence of NIR light irradiation, which agrees with the idea of the chemo-activity of DOXO predominating over the photothermal effect to induce cell death, favoring an apoptotic pathway over necrosis for cell death.
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Hipertermia Induzida , Nanotubos , Neoplasias , Humanos , Ouro , Células HeLa , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , FototerapiaRESUMO
Current treatment of chronic wounds has been critically limited by various factors, including bacterial infection, biofilm formation, impaired angiogenesis, and prolonged inflammation. Addressing these challenges, we developed a multifunctional wound dressing-based three-pronged approach for accelerating wound healing. The multifunctional wound dressing, composed of nanofibers, functional nanoparticles, natural biopolymers, and selected protein and peptide, can target multiple endogenous repair mechanisms and represents a promising alternative to current wound healing products.
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Anexina A1/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Bandagens , Diabetes Mellitus Experimental/complicações , Proteínas Relacionadas à Folistatina/administração & dosagem , Peptídeos/administração & dosagem , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Ferida Cirúrgica/complicações , Ferida Cirúrgica/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos/complicações , Infecção dos Ferimentos/tratamento farmacológico , Células 3T3 , Animais , Materiais Biocompatíveis/administração & dosagem , Biopolímeros/química , Sobrevivência Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/induzido quimicamente , Células HaCaT , Humanos , Nanopartículas Magnéticas de Óxido de Ferro/química , Masculino , Teste de Materiais/métodos , Camundongos , Nanofibras/química , Ratos , Ratos Wistar , Infecções Estafilocócicas/microbiologia , Resultado do Tratamento , Infecção dos Ferimentos/microbiologiaRESUMO
BACKGROUND: The unique upconversion properties of rare-earth-doped nanoparticles offers exciting opportunities for biomedical applications, in which near-IR remote activation of biological processes is desired, including in vivo bioimaging, optogenetics, and light-based therapies. Tuning of upconversion in purposely designed core-shell nanoparticles gives access to biological windows in biological tissue. In recent years there have been several reports on NIR-excitable upconverting nanoparticles capable of working in biological mixtures and cellular settings. Unfortunately, most of these nanosystems are based on ytterbium's upconversion at 980 nm, concurrent with water's absorption within the first biological window. Thus, methods to produce robust upconverting nanoplatforms that can be efficiently excited with other than 980 nm NIR sources, such as 808 nm and 1064 nm, are required for biomedical applications. RESULTS: Herein, we report a synthetic method to produce aqueous stable upconverting nanoparticles that can be activated with 808 nm excitation sources, thus avoiding unwanted heating processes due to water absorbance at 980 nm. Importantly, these nanoparticles, once transferred to an aqueous environment using an amphiphilic polymer, remain colloidally stable for long periods of time in relevant biological media, while keeping their photoluminescence properties. The selected polymer was covalently modified by click chemistry with two FDA-approved photosensitizers (Rose Bengal and Chlorin e6), which can be efficiently and simultaneously excited by the light emission of our upconverting nanoparticles. Thus, our polymer-functionalization strategy allows producing an 808 nm-activable photodynamic nanoplatform. These upconverting nanocomposites are preferentially stored in acidic lysosomal compartments, which does not negatively affect their performance as photodynamic agents. Upon 808 nm excitation, the production of reactive oxidative species (ROS) and their effect in mitochondrial integrity were demonstrated. CONCLUSIONS: In summary, we have demonstrated the feasibility of using photosensitizer-polymer-modified upconverting nanoplatforms that can be activated by 808 nm light excitation sources for application in photodynamic therapy. Our nanoplatforms remain photoactive after internalization by living cells, allowing for 808 nm-activated ROS generation. The versatility of our polymer-stabilization strategy promises a straightforward access to other derivatizations (for instance, by integrating other photosensitizers or homing ligands), which could synergistically operate as multifunctional photodynamic platforms nanoreactors for in vivo applications.
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Nanopartículas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Polímeros , Química Click , Estabilidade de Medicamentos , Células HeLa , Humanos , Raios Infravermelhos , Espaço Intracelular/química , Substâncias Luminescentes/química , Substâncias Luminescentes/farmacocinética , Substâncias Luminescentes/efeitos da radiação , Nanopartículas/química , Nanopartículas/metabolismo , Nanopartículas/efeitos da radiação , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacocinética , Fármacos Fotossensibilizantes/efeitos da radiação , Polímeros/química , Polímeros/farmacocinética , Polímeros/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismoRESUMO
The administration of small interfering RNA (siRNA) is a very interesting therapeutic option to treat genetic diseases such as Alzheimer's or some types of cancer, but its effective delivery still remains a challenge. Herein, Au nanorod (GNR)-based platforms functionalized with polyelectrolyte layers were developed and analyzed as potential siRNA nanocarriers. The polymeric layers were successfully assembled on the particle surfaces by means of the layer-by-layer assembly technique through the alternating deposition of oppositely charged poly(styrene)sulfonate, PSS, poly(lysine), PLL, and siRNA biopolymers, with a final hyaluronic acid layer in order to provide the nanoconstructs with a potential targeting ability as well as colloidal stability in physiological medium. Once the hybrid nanocarriers were obtained, the cargo release, their colloidal stability in physiological-relevant media, cytotoxicity, cellular internalization and uptake, and knockdown activity were studied. The present hybrid particles release the genetic material inside cells by means of a protease-assisted and/or a light-triggered release mechanism in order to control the delivery of the oligonucleotides on demand. In addition, the hybrid nanovectors were observed to be nontoxic to cells and could efficiently deliver the genetic material in the cell cytoplasms. The GNR-based nanocarriers proposed here can provide a suitable environment to load and protect a sufficient amount of the genetic material to allow an efficient and sustained knockdown gene expression for long (up to 93% for 72 h), thanks to the slow degradation of PLL, without the observation of adverse side toxic effects. It was also found that the silencing activity was enhanced with the number of siRNA layers assembled in the nanoplatforms.
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Portadores de Fármacos/química , Nanopartículas Metálicas/química , Neoplasias/terapia , RNA Interferente Pequeno/administração & dosagem , Terapêutica com RNAi/métodos , Técnicas de Silenciamento de Genes , Genes Reporter/genética , Ouro/química , Proteínas de Fluorescência Verde/genética , Células HeLa , Humanos , Nanotubos/química , Neoplasias/genética , Polilisina/química , Poliestirenos , RNA Interferente Pequeno/genéticaRESUMO
A plasmonic core-shell gold nanostar/zeolitic-imidazolate-framework-8 (ZIF-8) nanocomposite was developed for the thermoplasmonic-driven release of encapsulated active molecules inside living cells. The nanocomposites were loaded, as a proof of concept, with bisbenzimide molecules as functional cargo and wrapped with an amphiphilic polymer that prevents ZIF-8 degradation and bisbenzimide leaking in aqueous media or inside living cells. The demonstrated molecule-release mechanism relies on the use of near-IR light coupled to the plasmonic absorption of the core gold nanostars, which creates local temperature gradients and thus, bisbenzimide thermodiffusion. Confocal microscopy and surface-enhanced Raman spectroscopy (SERS) were used to demonstrate bisbenzimide loading/leaking and near-IR-triggered cargo release inside cells, thereby leading to DNA staining.
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A green, simple, and efficient room-temperature aqueous synthetic route for the fabrication of novel porous coordination polymer nanoparticles (NPs) composed of Cu2+ and imidazolate was developed. Colloidal stability, morphology changes, and structural and chemical integrity of the developed NPs, in several solvents having different polarity, were investigated. Basic physicochemical properties of selected NPs (i.e., NP1, NP2, and NP3), such as size, optical and magnetic activity, porosity, thermal stability, structure, aging, and catalytic activity, were determined. Data indicate that the addition of the surfactant hexadecyltrimethylammonium bromide (CTAB) and the final solvent determine the size, morphology, and structure of the different NPs.
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Some of the most prevalent neurodegenerative diseases are characterized by the accumulation of amyloid fibrils in organs and tissues. Although the pathogenic role of these fibrils has not been completely established, increasing evidence suggests off-pathway aggregation as a source of toxic/detoxicating deposits that still remains to be targeted. The present work is a step toward the development of off-pathway modulators using the same amyloid-specific dyes as those conventionally employed to screen amyloid inhibitors. We identified a series of kinetic signatures revealing the quantitative importance of off-pathway aggregation relative to amyloid fibrillization; these include non-linear semilog plots of amyloid progress curves, highly variable end point signals, and half-life coordinates weakly influenced by concentration. Molecules that attenuate/intensify the magnitude of these signals are considered promising off-pathway inhibitors/promoters. An illustrative example shows that amyloid deposits of lysozyme are only the tip of an iceberg hiding a crowd of insoluble aggregates. Thoroughly validated using advanced microscopy techniques and complementary measurements of dynamic light scattering, CD, and soluble protein depletion, the new analytical tools are compatible with the high-throughput methods currently employed in drug discovery.
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Amiloide/metabolismo , Amiloide/química , Dicroísmo Circular , Meia-Vida , Cinética , Agregados Proteicos , Estrutura Terciária de ProteínaRESUMO
Solid lipid nanoparticles (SLN) containing rifabutin (RFB), with pulmonary administration purposes, were developed through a technique that avoids the use of organic solvents or sonication. To facilitate their pulmonary delivery, the RFB-loaded SLN were included in microspheres of appropriate size using suitable excipients (mannitol and trehalose) through a spray-drying technique. Confocal analysis microscopy showed that microspheres are spherical and that SLN are efficiently microencapsulated and homogeneously distributed throughout the microsphere matrices. The aerodynamic diameters observed an optimal distribution for reaching the alveolar region. The dry powder's performance during aerosolization and the in vitro drug deposition were tested using a twin-impinger approach, which confirmed that the microspheres can reach the deep lung. Isothermal titration calorimetry revealed that SLN have higher affinity for mannitol than for trehalose. Upon microsphere dissolution in aqueous media, SLN were readily recovered, maintaining their physicochemical properties. When these dry powders reach the deep lung, microspheres are expected to readily dissolve, delivering the SLN which, in turn, will release RFB. The in vivo biodistribution of microencapsulated RFB-SLN demonstrated that the antibiotic achieved the tested organs 15 and 30 min post pulmonary administration. Their antimycobacterial activity was also evaluated in a murine model of infection with a Mycobacterium tuberculosis strain H37Rv resulting in an enhancement of activity against M. tuberculosis infection compared to nontreated animals. These results suggest that RFB-SLN microencapsulation is a promising approach for the treatment of tuberculosis.
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Antibacterianos/administração & dosagem , Antibacterianos/metabolismo , Lipídeos/química , Pulmão/metabolismo , Nanopartículas/química , Animais , Antibacterianos/uso terapêutico , Composição de Medicamentos , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Confocal , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/patogenicidade , Nanopartículas/administração & dosagem , Rifabutina/administração & dosagem , Rifabutina/metabolismo , Rifabutina/uso terapêuticoRESUMO
The objective of this study is to establish the ability of entrap allyl isothiocyanate (AITC) into polymeric nanoparticles to extend its shelf life and enhance its antiproliferative properties. Natural compounds, such as AITC, have showed multi-targeting activity resulting in a wide-range spectrum of therapeutic properties in chronic and degenerative diseases, conversely with most current pharmaceutical drugs showing single targeting activity and often result in drug resistance after extended administration periods. Apparently, AITC-loaded poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) reduced AITC degradation and volatility and were able to extend AITC shelf life compared with free AITC (65% vs. 20% in 24 h, respectively). Cell viability and uptake of AITC-loaded nanoparticles were studied in vitro, showing that the protection and sustained release of AITC from polymeric NPs involved a larger toxicity of tumoral cells. These nanoparticles could be used as protective systems for enhancing a biological activity.
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Preparações de Ação Retardada , Portadores de Fármacos/química , Isotiocianatos/administração & dosagem , Ácido Láctico/química , Nanopartículas/química , Ácido Poliglicólico/química , Linhagem Celular Tumoral , Humanos , Copolímero de Ácido Poliláctico e Ácido PoliglicólicoRESUMO
Amyloid fibrils and soluble oligomers are two types of protein aggregates associated with neurodegeneration. Classic therapeutic strategies try to prevent the nucleation and spread of amyloid fibrils, whilst diffusible oligomers have emerged as promising drug targets affecting downstream pathogenic processes. We developed a generic protein aggregation model and validate it against measured compositions of fibrillar and non-fibrillar assemblies of ataxin-3, a protein implicated in Machado-Joseph disease. The derived analytic rate-law equations can be used to 1)â identify the presence of parallel aggregation pathways and 2)â estimate the critical sizes of amyloid fibrils. The discretized population balance supporting our model is the first to quantitatively fit time-resolved measurements of size and composition of both amyloid-like and oligomeric species. The new theoretical framework can be used to screen a new class of drugs specifically targeting toxic oligomers.
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Amiloide/química , Proteínas/química , Ataxina-3/química , Biopolímeros/química , Cromatografia em Gel , Cinética , Microscopia Eletrônica de Transmissão , Ligação Proteica , Proteínas Repressoras/químicaRESUMO
Using an electrostatic-based super inkjet printer we report the high-resolution deposition of polyelectrolyte macroinitiators and subsequent polymer brush growth using SI-ARGET-ATRP. We go on to demonstrate for the first time a submicron patterning phenomenon through the addition of either a like charged polyelectrolyte homopolymer or through careful control of ionic strength. As a result patterning of polymer brushes down to ca. 300 nm is reported. We present a possible mechanistic model and consider how this may be applied to other polyelectrolyte-based systems as a general method for submicron patterning.
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It is well accepted that the surface modification of biomaterials can improve their biocompatibility. In this context, techniques like ion etching, plasma-mediated chemical functionalization, electrospinning, and contact microprinting have successfully been employed to promote the cell adhesion and proliferation of chitosan (CH) substrates. However, they prove to be time-consuming, highly dependent on environmental conditions, and/or limited to the use of expensive materials and sophisticated instruments not accessible to standard laboratories, hindering to a high extent their straightforward application. Filling this gap, this paper proposes the superficial cross-linking of CH as a much simpler and accessible means to modify its superficial properties in order to enhance its cellular affinity. CH membranes were prepared by solvent casting followed by a cross-linking step mediated by the chemical vapor deposition (CVD) of glutaraldehyde (GA). The membranes were characterized against non- and solution cross-linked membranes in terms of their mechanical/surface properties and biological performance. Among others, the CVD membranes proved (i) to be more mechanically stable against cell culture and sterilization than membranes cross-linked in solution and (ii) to prompt the adherence and sustained proliferation of healthy cells to levels even superior to commercial tissue culture plates (TCPs). Accordingly, the CVD cross-linking approach was demonstrated to be a simple and cost-effective alternative to the aforementioned conventional methods. Interestingly, this concept can also be applied to other biomaterials as long as GA (or other volatile components alike) can be employed as a cross-linker, making possible the cross-linking reaction at mild experimental conditions, neither requiring sophisticated lab implements nor using any potentially harmful procedure.
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Adesão Celular/fisiologia , Quitosana/química , Reagentes de Ligações Cruzadas/química , Membranas Artificiais , Sobrevivência Celular/fisiologia , Quitosana/metabolismo , Reagentes de Ligações Cruzadas/metabolismo , Células HeLa , Humanos , Ligação Proteica/fisiologiaRESUMO
Although the Classical Nucleation Theory (CNT) is the most consensual theory to explain protein nucleation mechanisms, experimental observations during the shear-induced assays suggest that the CNT does not always describe the insulin nucleation process. This is the case at intermediate precipitant (ZnCl2) solution concentrations (2.3 mM) and high-temperature values (20 and 40 °C) as well as at low precipitant solution concentrations (1.6 mM) and low-temperature values (5 °C). In this work, crystallization events following the CNT registered at high precipitant solution concentrations (3.1 and 4.7 mM) are typically described by a Newtonian response. On the other hand, crystallization events following a nonclassical nucleation pathway seem to involve the formation of a metastable intermediate state before crystal formation and are described by a transition from Newtonian to shear-thinning responses. A dominant shear-thinning behavior (shear viscosity values ranging more than 6 orders of magnitude) is found during aggregation/agglomeration events. The rheological analysis is complemented with different characterization techniques (Dynamic Light Scattering, Energy-Dispersive Spectroscopy, Circular Dichroism, and Differential Scanning Calorimetry) to understand the insulin behavior in solution, especially during the occurrence of aggregation/agglomeration events. To the best of our knowledge, the current work is the first study describing nonclassical nucleation mechanisms during shear-induced crystallization experiments, which reveals the potential of the interdisciplinary approach herein described and opens a window for a clear understanding of protein nucleation mechanisms.
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Urinary tract infections are commonly caused by uropathogenic Escherichia coli (UPEC), which usually presents multiple virulence and resistance mechanisms, making it difficult to treat. It has been demonstrated that silver and polymeric nanoparticles had potential against these pathogens. In this study, we synthesized thiol chitosan-coated silver nanoparticles (SH-Cs-AgNPs) and evaluated their antibacterial, antibiofilm and antiadherence activity against clinical isolates of UPEC. The SH-Cs-AgNPs showed a spherical shape with a size of 17.80 ± 2.67 nm and zeta potential of 18 ± 2 mV. We observed a potent antibacterial and antibiofilm activity as low as 12.5 µg/mL, as well as a reduction in the adherence of UPEC to mammalian cells at concentrations of 1.06 and 0.53 µg/mL. These findings demonstrate that SH-Cs-AgNPs have potential as a new therapeutic compound against infections caused by UPEC.
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Quitosana , Nanopartículas Metálicas , Escherichia coli Uropatogênica , Animais , Prata/farmacologia , Quitosana/farmacologia , Antibacterianos/farmacologia , Biofilmes , MamíferosRESUMO
Lanthanide-doped up-converting nanoparticles (UCNPs) have emerged as promising biomedical tools in recent years. Most research efforts were devoted to the synthesis of inorganic cores with the optimal physicochemical properties. However, the careful design of UCNPs with the adequate surface coating to optimize their biological performance still remains a significant challenge. Here, we propose the functionalization of UCNPs with four distinct types of surface coatings, which were compared in terms of the provided colloidal stability and resistance to degradation in different biological-relevant media, including commonly avoided analysis in acidic lysosomal-mimicking fluids. Moreover, the influence of the type of particle surface coating on cell cytotoxicity and endocytosis/exocytosis was also evaluated. The obtained results demonstrated that the functionalization of UCNPs with poly(isobutylene-alt-maleic anhydride) grafted with dodecylamine (PMA-g-dodecyl) constitutes an outstanding strategy for their subsequent biomedical application, whereas poly(ethylene glycol) (PEG) coating, although suitable for colloidal stability purposes, hinders extensive cell internalization. Conversely, surface coating with small ligand were found not to be suitable, leading to large degradation degrees of UCNPs. The analysis of particle' behavior in different biological media and in vitro conditions here performed pretends to help researchers to improve the design and implementation of UCNPs as theranostic nanotools.
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Endocitose , Nanopartículas , Propriedades de Superfície , Endocitose/efeitos dos fármacos , Humanos , Nanopartículas/química , Tamanho da Partícula , Sobrevivência Celular/efeitos dos fármacos , Polietilenoglicóis/químicaRESUMO
In this study, we consider segregative phase separation in aqueous mixtures of quaternary ammonium surfactants didecyldimethylammonium chloride (DDQ) and alkyl (C12, 70%; C14 30%) dimethyl benzyl ammonium chloride (BAC) upon the addition of poly(diallyldimethylammonium) chloride (pDADMAC) as a function of both concentration and molecular weight. The nature of the surfactant type is dominant in determining the concentration at which separation into an upper essentially surfactant-rich phase and lower polyelectrolyte-rich phase is observed. However, for high-molecular-weight pDADMAC there is a clear indication of an additional depletion flocculation effect. When the BAC/DDQ ratio is tuned, the segregative phase separation point can be precisely controlled. We propose a phase separation mechanism for like-charged quaternary ammonium polyelectrolyte/surfactant/water mixtures induced by a reduction in the ionic atmosphere around the surfactant headgroup and possible ion pair formation. An additional polyelectrolyte-induced depletion flocculation effect was also observed.
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Compostos de Benzalcônio/química , Polietilenos/química , Compostos de Amônio Quaternário/química , Tensoativos/química , Peso MolecularRESUMO
Scientific evidence increasingly supports the strong link between diet and health, acknowledging that a well-balanced diet plays a crucial role in preventing chronic diseases such as obesity, diabetes, cardiovascular issues, and certain types of cancer. This perspective opens the door to developing precision diets, particularly tailored for individuals at risk of developing cancer. It encompasses a vast research area and involves the study of an expanding array of compounds with multilevel "omics" compositions, including genomics, transcriptomics, proteomics, epigenomics, miRNomics, and metabolomics. We review here the components of the Southern European Atlantic Diet (SEAD) from both a chemical and pharmacological standpoint. The information sources consulted, complemented by crystallographic data from the Protein Data Bank, establish a direct link between the SEAD and its anticancer properties. The data collected strongly suggest that SEAD offers an exceptionally healthy profile, particularly due to the presence of beneficial biomolecules in its foods. The inclusion of olive oil and paprika in this diet provides numerous health benefits, and scientific evidence supports the anticancer properties of dietary supplements with biomolecules sourced from vegetables of the brassica genus. Nonetheless, further research is warranted in this field to gain deeper insights into the potential benefits of the SEAD's bioactive compounds against cancer.
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Dieta , Neoplasias , Humanos , Suplementos Nutricionais , Verduras , Antioxidantes , Neoplasias/prevenção & controleRESUMO
Conventional cancer therapies suffer from nonspecificity, drug resistance, and a poor bioavailability, which trigger severe side effects. To overcome these disadvantages, in this study, we designed and evaluated the in vitro potential of paclitaxel-loaded, PLGA-gold, half-shell nanoparticles (PTX-PLGA/Au-HS NPs) conjugated with cyclo(Arg-Gly-Asp-Phe-Lys) (cyRGDfk) as a targeted chemo-photothermal therapy system in HeLa and MDA-MB-231 cancer cells. A TEM analysis confirmed the successful gold half-shell structure formation. High-performance liquid chromatography showed an encapsulation efficiency of the paclitaxel inside nanoparticles of more than 90%. In the release study, an initial burst release of about 20% in the first 24 h was observed, followed by a sustained drug release for a period as long as 10 days, reaching values of about 92% and 49% for NPs with and without near infrared laser irradiation. In in vitro cell internalization studies, targeted nanoparticles showed a higher accumulation than nontargeted nanoparticles, possibly through a specific interaction of the cyRGDfk with their homologous receptors, the ανß3 y ανß5 integrins on the cell surface. Compared with chemotherapy or photothermal treatment alone, the combined treatment demonstrated a synergistic effect, reducing the cell viability to 23% for the HeLa cells and 31% for the MDA-MB-231 cells. Thus, our results indicate that these multifuncional nanoparticles can be considered to be a promising targeted chemo-photothermal therapy system against cancer.
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Gold nanorods (AuNRs) have attracted attention in the field of biomedicine, particularly for their potential as photothermal agents capable of killing tumor cells by photothermic ablation. In this study, the synthesis of novel AuNRs stabilized with thiolated pectin (AuNR@SH-PEC) is reported. To achieve this, thiolated pectin (SH-PEC) was obtained by chemically binding cysteamine motifs to the pectin backbone. The success of the reaction was ascertained using FTIR-ATR. Subsequently, the SH-PEC was used to coat and stabilize the surface of AuNRs (AuNR@SH-PEC). In this context, different concentrations of SH-PEC (0.25, 0.50, 1.0, 2.0, 4.0, and 8.0 mg/mL) were added to 0.50 mL of AuNRs suspended in CTAB, aiming to determine the experimental conditions under which AuNR@SH-PEC maintains stability. The results show that SH-PEC effectively replaced the CTAB adsorbed on the surface of AuNRs, enhancing the stability of AuNRs without affecting their optical properties. Additionally, scanning electron and atomic force microscopy confirmed that SH-PEC is adsorbed into the surface of the AuNRs. Importantly, the dimension size (60 × 15 nm) and the aspect ratio (4:1) remained consistent with those of AuNRs stabilized with CTAB. Then, the photothermal properties of gold nanorods were evaluated by irradiating the aqueous suspension of AuNR@SH-PEC with a CW laser (808 nm, 1 W). These results showed that photothermal conversion efficiency is similar to the photothermal conversion observed for AuNR-CTAB. Lastly, the cell viability assays confirmed that the SH-PEC coating enhanced the biocompatibility of AuNR@SH-PEC. Most important, the viability cell assays subjected to laser irradiation in the presence of AuNR@SH-PEC showed a decrease in the cell viability relative to the non-irradiated cells. These results suggest that AuNRs stabilized with thiolated pectin can potentially be exploited in the implementation of photothermal therapy.