RESUMO
The main cause of subretinal neovascularisation in wet age-related macular degeneration (AMD) is an abnormal expression in the retinal pigment epithelium (RPE) of the vascular endothelial growth factor (VEGF). Current approaches for the treatment of AMD present considerable issues that could be overcome by encapsulating anti-VEGF drugs in suitable nanocarriers, thus providing better penetration, higher retention times, and sustained release. In this work, the ability of large pore mesoporous silica nanoparticles (LP-MSNs) to transport and protect nucleic acid molecules is exploited to develop an innovative LP-MSN-based nanosystem for the topical administration of anti-VEGF siRNA molecules to RPE cells. siRNA is loaded into LP-MSN mesopores, while the external surface of the nanodevices is functionalised with polyethylenimine (PEI) chains that allow the controlled release of siRNA and promote endosomal escape to facilitate cytosolic delivery of the cargo. The successful results obtained for VEGF silencing in ARPE-19 RPE cells demonstrate that the designed nanodevice is suitable as an siRNA transporter.
Assuntos
Nanopartículas , Fator A de Crescimento do Endotélio Vascular , RNA Interferente Pequeno/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Dióxido de Silício/metabolismo , Epitélio Pigmentado da Retina/metabolismoRESUMO
Cancer-related opportunistic bacterial infections are one major barrier for successful clinical therapies, often correlated to the production of genotoxic factors and higher cancer incidence. Although dual anticancer and antimicrobial therapies are a growing therapeutic fashion, they still fall short when it comes to specific delivery and local action in in vivo systems. Nanoparticles are seen as potential therapeutic vectors, be it by means of their intrinsic antibacterial properties and effective delivery capacity, or by means of their repeatedly reported modulation and maneuverability. Herein we report on the production of a biocompatible, antimicrobial magneto-fluorescent nanosystem (NANO3) for the delivery of a dual doxorubicin-ofloxacin formulation against cancer-related bacterial infections. The drug delivery capacity, rendered by its mesoporous silica matrix, is confirmed by the high loading capacity and stimuli-driven release of both drugs, with preference for tumor-like acidic media. The pH-dependent emission of its surface fluorescent SiQDs, provides an insight into NANO3 surface behavior and pore availability, with the SiQDs working as pore gates. Hyperthermia induces heat generation to febrile temperatures, doubling drug release. NANO3-loaded systems demonstrate significant antimicrobial activity, specifically after the application of hyperthermia conditions. NANO3 structure and antimicrobial properties confirm their potential use in a future dual anticancer and antimicrobial therapeutical vector, due to their drug loading capacity and their surface availability for further modification with bioactive, targeting species.
Assuntos
Anti-Infecciosos , Neoplasias Colorretais , Hipertermia Induzida , Nanopartículas , Humanos , Portadores de Fármacos/química , Ofloxacino , Porosidade , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Doxorrubicina/química , Dióxido de Silício/química , Nanopartículas/química , Liberação Controlada de Fármacos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Sistemas de Liberação de MedicamentosRESUMO
Inâ vivo detection of cellular senescence is accomplished by using mesoporous silica nanoparticles loaded with the NIR-FDA approved Nile blue (NB) dye and capped with a galactohexasaccharide (S3). NB emission at 672â nm is highly quenched inside S3, yet a remarkable emission enhancement is observed upon cap hydrolysis in the presence of ß-galactosidase and dye release. The efficacy of the probe to detect cellular senescence is tested inâ vitro in melanoma SK-Mel-103 and breast cancer 4T1 cells and inâ vivo in palbociclib-treated BALB/cByJ mice bearing breast cancer tumor.
Assuntos
Senescência Celular/imunologia , Corantes Fluorescentes/uso terapêutico , Animais , Feminino , Humanos , Camundongos , OxazinasRESUMO
Janus gold nanostar-mesoporous silica nanoparticle (AuNSt-MSNP) nanodevices able to release an entrapped payload upon irradiation with near infrared (NIR) light were prepared and characterized. The AuNSt surface was functionalized with a thiolated photolabile molecule (5), whereas the mesoporous silica face was loaded with a model drug (doxorubicin) and capped with proton-responsive benzimidazole-ß-cyclodextrin supramolecular gatekeepers (N 1). Upon irradiation with NIR-light, the photolabile compound 5 photodissociated, resulting in the formation of succinic acid, which induced the opening of the gatekeeper and cargo delivery. In the overall mechanism, the gold surface acts as a photochemical transducer capable of transforming the NIR-light input into a chemical messenger (succinic acid) that opens the supramolecular nanovalve. The prepared hybrid nanoparticles were non-cytotoxic to HeLa cells, until they were irradiated with a NIR laser, which led to intracellular doxorubicin release and hyperthermia. This induced a remarkable reduction in HeLa cells viability.
Assuntos
Portadores de Fármacos/química , Ouro/química , Raios Infravermelhos , Nanoestruturas/química , Dióxido de Silício/química , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Doxorrubicina/metabolismo , Doxorrubicina/farmacologia , Humanos , Hipertermia Induzida , Microscopia Confocal , Nanoestruturas/toxicidade , PorosidadeRESUMO
This work reports a new gated nanodevice for acetylcholine-triggered cargo delivery. We prepared and characterized Janus Au-mesoporous silica nanoparticles functionalized with acetylcholinesterase on the Au face and with supramolecular ß-cyclodextrin:benzimidazole inclusion complexes as caps on the mesoporous silica face. The nanodevice is able to selectively deliver the cargo in the presence of acetylcholine via enzyme-mediated acetylcholine hydrolysis, locally lowering the pH and opening the supramolecular gate. Given the key role played by ACh and its relation with Parkinson's disease and other nervous system diseases, we believe that these findings could help design new therapeutic strategies.
Assuntos
Acetilcolinesterase/metabolismo , Portadores de Fármacos/química , Ouro/química , Nanopartículas/química , Dióxido de Silício/química , Acetilcolina/metabolismo , Acetilcolinesterase/química , Benzimidazóis/química , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Doxorrubicina/metabolismo , Doxorrubicina/toxicidade , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Hidrólise , Compostos Organometálicos/química , Compostos Organometálicos/metabolismo , Porosidade , beta-Ciclodextrinas/químicaRESUMO
Chemical burns, mainly produced by acids, are a topic of concern. A new sensing material for the detection of strong acids able to be incorporated into textiles has been developed. The material is prepared by the covalent attachment of 2,2',4,4',4â³-pentamethoxy triphenyl methanol to a mesoporous material which further is included in a nitro resin to obtain a colourless composite. The response of this composite to diverse acid solutions was tested showing the appearance of an intense purple colour (with a colour difference higher than 160) that can be monitored by the naked eye or could be easily digitised to feed an instrumental sensor. Reversibility and resistance to washing cycles were studied with positive results. Finally, the response of the sensing composite to acid vapours was assayed, observing a colour change similar to that found in solution.
RESUMO
New capped silica mesoporous nanoparticles for intracellular controlled cargo release within cathepsinâ B expressing cells are described. Nanometric mesoporous MCM-41 supports loaded with safraninâ O (S1-P) or doxorubicin (S2-P) containing a molecular gate based on a cathepsinâ B target peptidic sequence were synthesized. Solids were designed to show "zero delivery" and to display cargo release in the presence of cathepsinâ B enzyme, which selectively hydrolyzed in vitro the capping peptide sequence. Controlled delivery in HeLa, MEFs WT, and MEFs lacking cathepsinâ B cell lines were also tested. Release of safraninâ O and doxorubicin in these cells took place when cathepsinâ B was active or present. Cells treated with S2-P showed a fall in cell viability due to nanoparticles internalization, cathepsinâ B hydrolysis of the capping peptide, and cytotoxic agent delivery, proving the possible use of these nanodevices as new therapeutic tools for cancer treatment.
Assuntos
Catepsina B/metabolismo , Nanopartículas/química , Peptídeos/química , Dióxido de Silício/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Células HeLa , Humanos , Peptídeos/síntese química , Peptídeos/metabolismo , PorosidadeRESUMO
Bug busters: A novel nanodevice consisting of mesoporous nanoparticles loaded with vancomycin and capped with ε-poly-L-lysine (ε-PL) was prepared and its interaction with different Gram-negative bacteria studied. A remarkable improvement in the efficacy of the antimicrobial drug ε-PL and a broadening of the antimicrobial spectrum of vancomycin is demonstrated.
Assuntos
Antibacterianos/química , Nanopartículas/química , Vancomicina/química , Antibacterianos/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Polilisina/química , Porosidade , Dióxido de Silício/químicaRESUMO
This critical review is focused on examples reported from 1947 to 2010 related to the design of chromo-fluorogenic chemosensors and reagents for explosives (141 references).
Assuntos
Técnicas de Química Analítica/instrumentação , Substâncias Explosivas/análise , Fenômenos Ópticos , Colorimetria , Substâncias Explosivas/química , Indicadores e Reagentes/química , Espectrometria de FluorescênciaRESUMO
In water and wine: Chromofluorogenic detection of the sulfite anion in pure water was accomplished by using a new hybrid organic-inorganic material that contained a probe entrapped in hydrophobic biomimetic cavities. This material was used for the detection of sulfite in red wine.
RESUMO
This work reports on the synthesis of nine materials containing Cu, Ag, Au, and Ag/Cu nanoparticles (NPs) deposited on magnetite particles coated with polydopamine (PDA). Ag NPs were deposited on two PDA@Fe3O4 supports differing in the thickness of the PDA film. The film thickness was adjusted to impart a textural porosity to the material. During synthesis, Ag(I) was reduced with ascorbic acid (HA), photochemically, or with NaBH4, whereas Au(III), with HA, with the PDA cathecol groups, or NaBH4. For the material characterization, TGA, XRD, SEM, EDX, TEM, STEM-HAADF, and DLS were used. The catalytic activity towards reduction of 4-, 3- and 2-nitrophenol was tested and correlated with the synthesis method, film thickness, metal particle size and NO2 group position. An evaluation of the recyclability of the materials was carried out. In general, the catalysts prepared by using soft reducing agents and/or thin PDA films were the most active, while the materials reduced with NaBH4 remained unchanged longer in the reactor. The activity varied in the direction Au > Ag > Cu. However, the Ag-based materials showed a higher recyclability than those based on gold. It is worth noting that the Cu-containing catalyst, the most environmentally friendly, was as active as the best Ag-based catalyst.
RESUMO
The development of nanomaterials that mimic the activity of enzymes is a topic of interest, for the decomposition of reactive oxygen species (ROS). We report the preparation of a novel nanocomposite of MnOx needles covered with SiO2 porous material. The material was prepared in one pot with a two-step procedure. The material was characterized by EDX, SEM, TEM, XRD, nitrogen adsorption-desorption isotherms, and XPS. The synthesis protocol took advantage of the atrane method, favoring the nucleation and initial growth of manganese oxide needles that remained embedded and homogeneously dispersed in a mesoporous silica matrix. The final composite had a high concentration of Mn (Si/Mn molar ratio of ca. 1). The nanozyme presented bimodal porosity: intraparticle and interparticle association with the surfactant micelles and the gaps between silica particles and MnOx needles, respectively. The porosity favored the migration of the reagent to the surface of the catalytic MnOx. The nanozyme showed very efficient SOD and catalase activities, thus improving other materials previously described. The kinetics were studied in detail, and the reaction mechanisms were proposed. It was shown that silica does not play an innocent role in the case of catalase activity, increasing the reaction rate.
RESUMO
Acute lung injury (ALI) is a critical inflammatory syndrome, characterized by increased diffuse inflammation and severe lung damage, which represents a clinical concern due to the high morbidity and mortality in critical patients. In last years, there has been a need to develop more effective treatments for ALI, and targeted drug delivery to inflamed lungs has become an attractive research field. Here, we present a nanodevice based on mesoporous silica nanoparticles loaded with dexamethasone (a glucocorticoid extensively used for ALI treatment) and capped with a peptide that targets the TNFR1 receptor expressed in pro-inflammatory macrophages (TNFR-Dex-MSNs) and avoids cargo leakage. TNFR-Dex-MSNs nanoparticles are preferentially internalized by pro-inflammatory macrophages, which overexpressed the TNFR1 receptor, with the subsequent cargo release upon the enzymatic hydrolysis of the capping peptide in lysosomes. Moreover, TNFR-Dex-MSNs are able to reduce the levels of TNF-α and IL-1ß cytokines in activated pro-inflammatory M1 macrophages. The anti-inflammatory effect of TNFR-Dex-MSNs is also tested in an in vivo ALI mice model. The administered nanodevice (intravenously by tail vein injection) accumulated in the injured lungs and the controlled dexamethasone release reduces markedly the inflammatory response (TNF-α IL-6 and IL-1ß levels). The attenuation in lung damage, after treatment with TNFR-Dex-MSNs, is also confirmed by histopathological studies. Besides, the targeted-lung dexamethasone delivery results in a decrease of dexamethasone derived side-effects, suggesting that targeted nanoparticles can be used for therapy in ALI and could help to overcome the clinical limitations of current treatments.
Assuntos
Lesão Pulmonar Aguda , Nanopartículas , Lesão Pulmonar Aguda/tratamento farmacológico , Animais , Dexametasona , Humanos , Pulmão , Camundongos , Dióxido de SilícioRESUMO
The characteristics and electromechanical properties of conductive polymers together to their biocompatibility have boosted their application as a suitable tool in regenerative medicine and tissue engineering. However, conducting polymers as drug release materials are far from being ideal. A possibility to overcome this drawback is to combine conducting polymers with on-command delivery particles with inherent high-loading capacity. In this scenario, we report here the preparation of conduction polymers containing gated mesoporous silica nanoparticles (MSN) loaded with a cargo that is delivered on command by electro-chemical stimuli increasing the potential use of conducting polymers as controlled delivery systems. MSNs are loaded with Rhodamine B (Rh B), anchored to the conductive polymer poly(3,4-ethylenedioxythiophene) (PEDOT) doped with poly[(4-styrenesulfonic acid)-co-(maleic acid)], functionalized with a bipyridinium derivative and pores are capped with heparin (P3) by electrostatic interactions. P3 releases the entrapped cargo after the application of -640â¯mV voltage versus the saturated calomel electrode (SCE). Pore opening in the nanoparticles and dye delivery is ascribed to both (i) the reduction of the grafted bipyridinium derivative and (ii) the polarization of the conducting polymer electrode to negative potentials that induce detachment of positively charged heparin from the surface of the nanoparticles. Biocompatibility and cargo release studies were carried out in HeLa cells cultures.
Assuntos
Nanopartículas , Dióxido de Silício , Compostos Bicíclicos Heterocíclicos com Pontes , Células HeLa , Humanos , Polímeros , PorosidadeRESUMO
Silica nanoparticles functionalized with chromogenic spirobenzopyran and thiourea subunits show selective colour changes in the presence of certain long-chain carboxylates.
RESUMO
The objective of this work was on the one hand to assess the antibacterial activity of amines anchored to the external surface of mesoporous silica particles against Listeria monocytogenes in comparison with the same dose of free amines as well. It was also our aim to elucidate the mechanism of action of the new antimicrobial device. The suitability of silica nanoparticles to anchor, concentrate and improve the antimicrobial power of polyamines against L. monocytogenes has been demonstrated in a saline solution and in a food matrix. Moreover, through microscope observations it has been possible to determine that the attractive binding forces between the positive amine corona on the surface of nanoparticles and the negatively charged bacteria membrane provoke a disruption of the cell membrane. The surface concentration of amines on the surface of the nanoparticles is so effective that immobilized-amines were 100 times more effective in killing L. monocytogenes bacteria than the same amount of free polyamines. This novel approach for the creation of antimicrobial nanodevices opens the possibility to put in value the antimicrobial power of natural molecules that have been discarded because of its low antimicrobial power. PRACTICAL APPLICATION: Consumers demand for high-quality products, free from chemical preservatives, with an extended shelf-life. In this study, a really powerful antimicrobial agent based on a nanomaterial functionalized with a non-antimicrobial organic molecule was developed as a proof of concept. Following this approach it could be possible to develop a new generation of natural and removable antimicrobials based on their anchoring to functional surfaces for food, agricultural or medical purposes.
Assuntos
Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Nanotecnologia/métodos , Aminas/química , Aminas/farmacologia , Antibacterianos/química , Anti-Infecciosos/química , Microbiologia de Alimentos , Conservantes de Alimentos/farmacologia , Listeria monocytogenes/efeitos dos fármacos , Nanopartículas/química , Dióxido de Silício/química , Relação Estrutura-AtividadeRESUMO
Organic-inorganic hybrid nanomaterials offer extremely valuable tools for monitoring many types of analytes in solution. Within this framework, aptamer-based nanomaterials for heavy metal detection are still very scarce. Herein, a novel sensing nanoprobe for the selective and sensitive detection of As(III) based on the combination of aptamers with mesoporous silica nanoparticles has been developed. The efficiency of the sensor is demonstrated in environmental conditions, showing a great potential in As(III) monitoring assays.
RESUMO
Two different acetylcholinesterase (AChE)-capped mesoporous silica nanoparticles (MSNs), S1-AChE and S2-AChE, were prepared and characterized. MSNs were loaded with rhodamineâ B and the external surface was functionalized with either pyridostigmine derivative P1 (to yield solid S1) or neostigmine derivative P2 (to obtain S2). The final capped materials were obtained by coordinating grafted P1 or P2 with AChE's active sites (to give S1-AChE and S2-AChE, respectively). Both materials were able to release rhodamineâ B in the presence of diisopropylfluorophosphate (DFP) or neostigmine in a concentration-dependent manner via the competitive displacement of AChE through DFP and neostigmine coordination with the AChE's active sites. The responses of S1-AChE and S2-AChE were also tested with other enzyme inhibitors and substrates. These studies suggest that S1-AChE nanoparticles can be used for the selective detection of nerve agent simulant DFP and paraoxon.
Assuntos
Acetilcolinesterase/química , Inibidores Enzimáticos/farmacologia , Nanopartículas/química , Dióxido de Silício/química , Domínio Catalítico , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/química , Isoflurofato/química , Isoflurofato/farmacologia , Porosidade , Rodaminas/química , Propriedades de SuperfícieRESUMO
Folic acid (FA) is a synthetic vitamin commonly used for food fortification. However, its vulnerability to processing and storage implies loss of efficiency, which would induce over-fortification by processors to obtain a minimum dose upon consumption. Recent studies have indicated potential adverse effects of FA overdoses, and FA protection during processing and storage could lead to more accurate fortification. In addition, sustained vitamin release after consumption would help improve its metabolism. The objective of this work was to study controlled FA delivery and stability in fruit juices to reduce potential over-fortification risks by using gated mesoporous silica particles (MSPs). The obtained results indicated that FA encapsulation in MSPs significantly improved its stability and contributed to controlled release after consumption by modifying vitamin bioaccessibility. These results confirmed the suitability of MSPs as support for controlled release and protection of bioactive molecules in food matrices in different food production and storage stages.