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1.
Nat Commun ; 15(1): 487, 2024 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-38216556

RESUMEN

Periodontal disease is a significant burden for oral health, causing progressive and irreversible damage to the support structure of the tooth. This complex structure, the periodontium, is composed of interconnected soft and mineralised tissues, posing a challenge for regenerative approaches. Materials combining silicon and lithium are widely studied in periodontal regeneration, as they stimulate bone repair via silicic acid release while providing regenerative stimuli through lithium activation of the Wnt/ß-catenin pathway. Yet, existing materials for combined lithium and silicon release have limited control over ion release amounts and kinetics. Porous silicon can provide controlled silicic acid release, inducing osteogenesis to support bone regeneration. Prelithiation, a strategy developed for battery technology, can introduce large, controllable amounts of lithium within porous silicon, but yields a highly reactive material, unsuitable for biomedicine. This work debuts a strategy to lithiate porous silicon nanowires (LipSiNs) which generates a biocompatible and bioresorbable material. LipSiNs incorporate lithium to between 1% and 40% of silicon content, releasing lithium and silicic acid in a tailorable fashion from days to weeks. LipSiNs combine osteogenic, cementogenic and Wnt/ß-catenin stimuli to regenerate bone, cementum and periodontal ligament fibres in a murine periodontal defect.


Asunto(s)
Nanocables , beta Catenina , Animales , Ratones , Silicio/farmacología , Porosidad , Litio/farmacología , Ácido Silícico/farmacología , Cemento Dental
2.
Data Brief ; 48: 109285, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37383788

RESUMEN

This dataset contains expert assessments of the cybersecurity skills required for six job profiles in Europe, as determined via surveys responded by cybersecurity experts from academia and industry. The data can be used to identify educational needs in the cybersecurity sector and compare against other frameworks. The six cybersecurity-oriented job profiles used in the surveys are: General cybersec auditor; Technical cybersec auditor; Threat modelling engineer; Security engineer; Enterprise cybersecurity practitioner; Cybersecurity analyst. Data-i.e. expert assessments-was collected via surveys, targeted at European experts in cybersecurity from academia and industry. Respondents characterised the skills needed to perform in six job profiles using the CSEC+ framework: a cybersecurity skills framework prepared as a spreadsheet where cybersecurity skills must be ranked in a Likert scale from 0 (irrelevant) to 4 (advance knowledge needed). Metadata requested included the type of organisation of the respondent (Large company, SME, Academic/Research, Public administration, Other) and the country of origin. There were three data-collection phases: (1) an initial phase, used also to refine later larger-scale processes, carried out in Oct 2021-Jan 2022 and resulting in 13 expert assessments from four EU countries; (2) a second phase implemented as an online service broadcast to a larger audience, carried out in Mar-Apr 2022 and resulting in 15 assessments from eight European countries; (3) and a third phase, allowing direct online input and distributed in PC and mobile form, carried out in Sep-Oct 2022 and resulting in 32 assessments from ten European countries. The raw data gathered was stored and processed via spreadsheets, computing statistical information (mean, stdev) on how much each cybersecurity skill and area was deemed necessary to perform in each job profile. This is visualised as a heatmap where colour intensity symbolises value, and circle diffusion symbolises spread. Processed data further includes visualisations on how the area of origin of the respondent (academia, as in "producer of education", vs. industry, as in "consumer of education") influences the responses. This is shown as bar plots, where whiskers represent confidence intervals used for statistical-significance tests. This data can serve as basis to understand the educational needs for the cybersecurity sector in Europe. It can be reused for comparison against frameworks, other than CSEC+, to assess the need of education in specific cybersecurity sectors such as human security. Furthermore, the Qualtrics survey template (included) is a ready-made solution for replication studies.

3.
Adv Mater ; 34(42): e2203915, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35985348

RESUMEN

As a result of the deficient tumor-specific antigens, potential off-target effect, and influence of protein corona, metal-organic framework nanoparticles have inadequate accumulation in tumor tissues, limiting their therapeutic effects. In this work, a pH-responsive linker (L) is prepared by covalently modifying oleylamine (OA) with 3-(bromomethyl)-4-methyl-2,5-furandione (MMfu) and poly(ethylene glycol) (PEG). Then, the L is embedded into a solid lipid nanoshell to coat apilimod (Ap)-loaded zeolitic imidazolate framework (Ap-ZIF) to form Ap-ZIF@SLN#L. Under the tumor microenvironment, the hydrophilic PEG and MMfu are removed, exposing the hydrophobic OA on Ap-ZIF@SLN#L, increasing their uptake in cancer cells and accumulation in the tumor. The ZIF@SLN#L nanoparticle induces reactive oxygen species (ROS). Ap released from Ap-ZIF@SLN#L significantly promotes intracellular ROS and lactate dehydrogenase generation. Ap-ZIF@SLN#L inhibits tumor growth, increases the survival rate in mice, activates the tumor microenvironment, and improves the infiltration of macrophages and T cells in the tumor, as demonstrated in two different tumor-bearing mice after injections with Ap-ZIF@SLN#TL. Furthermore, mice show normal tissue structure of the main organs and the normal serum level in alanine aminotransferase and aspartate aminotransferase after treatment with the nanoparticles. Overall, this pH-responsive targeting strategy improves nanoparticle accumulation in tumors with enhanced therapeutic effects.


Asunto(s)
Estructuras Metalorgánicas , Nanopartículas , Neoplasias , Corona de Proteínas , Zeolitas , Ratones , Animales , Estructuras Metalorgánicas/química , Especies Reactivas de Oxígeno , Alanina Transaminasa , Anhídridos Maleicos , Nanopartículas/química , Zeolitas/química , Neoplasias/tratamiento farmacológico , Polietilenglicoles/química , Concentración de Iones de Hidrógeno , Aspartato Aminotransferasas , Lactato Deshidrogenasas , Lípidos , Microambiente Tumoral
4.
Int J Pharm ; 624: 121959, 2022 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-35792422

RESUMEN

Many drugs with anticancer potential fail in their translation to the clinics due to problems related to pharmacokinetics. LEM2 is a new dual inhibitor of MDM2/mutp53-TAp73 interactions with interesting in vitro anticancer activity, which opens new hopes as an unconventional anticancer therapeutic strategy against cancers lacking p53 or with impaired p53 pathways. As others xanthone derivatives, LEM2 has limited aqueous solubility, posing problems to pursue in vivo assays, and therefore limiting its potential clinical translation. In this work, a mesoporous silicon (PSi)-based nanodelivery system was developed with folate functionalization (APTES-TCPSi-PEG-FA) for targeted delivery, which successfully increased LEM2 solubility when compared to bulk LEM2, evidenced in payload release study. Such effect was reflected on the increase of LEM2 cytotoxicity in HCT116 and MDA-MB-231 cancer cells when treated with LEM2-loaded APTES-TCPSi-PEG-FA, by reducing cell viability lower than 50% in comparison with bulk LEM2. Despite the reduced LEM2 loading degree, which still limits its application in further in vivo assays, the results obtained herein recognize PSi-based nanodelivery systems as a promising strategy to improve LEM2 anticancer activity and bioavailability, which will be relevant for the potential use of this potent TAp73 activator in anticancer therapy.


Asunto(s)
Antineoplásicos , Nanopartículas , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Ácido Fólico , Silicio , Dióxido de Silicio , Proteína p53 Supresora de Tumor
5.
ACS Biomater Sci Eng ; 8(10): 4132-4139, 2022 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-34292713

RESUMEN

Porous silicon (PSi) nanoparticles have been applied in various fields, such as catalysis, imaging, and biomedical applications, because of their large specific surface area, easily modifiable surface chemistry, biocompatibility, and biodegradability. For biomedical applications, it is important to precisely control the surface modification of PSi-based materials and quantify the functionalization density, which determines the nanoparticle's behavior in the biological system. Therefore, we propose here an optimized solution to quantify the functionalization groups on PSi, based on the nuclear magnetic resonance (NMR) method by combining the hydrolysis with standard 1H NMR experiments. We optimized the hydrolysis conditions to degrade the PSi, providing mobility to the molecules for NMR detection. The NMR parameters were also optimized by relaxation delay and the number of scans to provide reliable NMR spectra. With an internal standard, we quantitatively analyzed the surficial amine groups and their sequential modification of polyethylene glycol. Our investigation provides a reliable, fast, and straightforward method in quantitative analysis of the surficial modification characterization of PSi requiring a small amount of sample.


Asunto(s)
Nanopartículas , Silicio , Aminas , Nanopartículas/química , Polietilenglicoles , Porosidad , Espectroscopía de Protones por Resonancia Magnética , Silicio/química
6.
Bioact Mater ; 9: 299-315, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34820572

RESUMEN

Oral insulin delivery could change the life of millions of diabetic patients as an effective, safe, easy-to-use, and affordable alternative to insulin injections, known by an inherently thwarted patient compliance. Here, we designed a multistage nanoparticle (NP) system capable of circumventing the biological barriers that lead to poor drug absorption and bioavailability after oral administration. The nanosystem consists of an insulin-loaded porous silicon NP encapsulated into a pH-responsive lignin matrix, and surface-functionalized with the Fc fragment of immunoglobulin G, which acts as a targeting ligand for the neonatal Fc receptor (FcRn). The developed NPs presented small size (211 ± 1 nm) and narrow size distribution. The NPs remained intact in stomach and intestinal pH conditions, releasing the drug exclusively at pH 7.4, which mimics blood circulation. This formulation showed to be highly cytocompatible, and surface plasmon resonance studies demonstrated that FcRn-targeted NPs present higher capacity to interact and being internalized by the Caco-2 cells, which express FcRn, as demonstrated by Western blot. Ultimately, in vitro permeability studies showed that Fc-functionalized NPs induced an increase in the amount of insulin that permeated across a Caco-2/HT29-MTX co-culture model, showing apparent permeability coefficients (P app ) of 2.37 × 10-6 cm/s, over the 1.66 × 10-6 cm/s observed for their non-functionalized counterparts. Overall, these results demonstrate the potential of these NPs for oral delivery of anti-diabetic drugs.

7.
Adv Mater ; 34(9): e2108012, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34877724

RESUMEN

An alternative strategy of choosing photothermal and weak-immunostimulatory porous silicon@Au nanocomposites as particulate cores to prepare a biomimetic nanovaccine is reported to improve its biosafety and immunotherapeutic efficacy for solid tumors. A quantitative analysis method is used to calculate the loading amount of cancer cell membranes onto porous silicon@Au nanocomposites. Assisted with foreign-body responses, these exogenous nanoparticulate cores with weak immunostimulatory effect can still efficiently deliver cancer cell membranes into dendritic cells to activate them and the downstream antitumor immunity, resulting in no occurrence of solid tumors and the survival of all immunized mice during 55 day observation. In addition, this nanovaccine, as a photothermal therapeutic agent, synergized with additional immunotherapies can significantly inhibit the growth and metastasis of established solid tumors, via the initiation of the antitumor immune responses in the body and the reversion of their immunosuppressive microenvironments. Considering the versatile surface engineering of porous silicon nanoparticles, the strategy developed here is beneficial to construct multifunctional nanovaccines with better biosafety and more diagnosis or therapeutic modalities against the occurrence, recurrence, or metastasis of solid tumors in future clinical practice.


Asunto(s)
Nanocompuestos , Nanopartículas , Neoplasias , Animales , Biomimética/métodos , Inmunoterapia , Ratones , Nanopartículas/uso terapéutico , Neoplasias/terapia , Microambiente Tumoral
8.
Mol Nutr Food Res ; 66(4): e2100978, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34882959

RESUMEN

SCOPE: Nutrients stimulate the secretion of glucagon-like peptide-1 (GLP-1), an incretin hormone, secreted from enteroendocrine L-cells which decreases food intake. Thus, GLP-1 analogs are approved for the treatment of obesity, yet cost and side effects limit their use. L-cells are mainly localized in the distal ileum and colon, which hinders the utilization of nutrients targeting GLP-1 secretion. This study proposes a controlled delivery system for nutrients, inducing a prolonged endogenous GLP-1 release which results in a decrease food intake. METHODS AND RESULTS: α-Linolenic acid (αLA) was loaded into thermally hydrocarbonized porous silicon (THCPSi) particles. In vitro characterization and in vivo effects of αLA loaded particles on GLP-1 secretion and food intake were studied in mice. A total of 40.4 ± 3.2% of loaded αLA is released from particles into biorelevant buffer over 24 h, and αLA loaded THCPSi significantly increased in vitro GLP-1 secretion. Single-dose orally given αLA loaded mesoporous particles increased plasma active GLP-1 levels at 3 and 4 h and significantly reduced the area under the curve of 24 h food intake in mice. CONCLUSIONS: αLA loaded THCPSi particles could be used to endogenously stimulate sustain gastrointestinal hormone release and reduce food intake.


Asunto(s)
Péptido 1 Similar al Glucagón , Ácido alfa-Linolénico , Animales , Colon , Ingestión de Alimentos , Ratones , Nutrientes , Ácido alfa-Linolénico/farmacología
9.
Cell Rep ; 35(8): 109131, 2021 05 25.
Artículo en Inglés | MEDLINE | ID: mdl-34038723

RESUMEN

Communication between biological components is critical for homeostasis maintenance among the convergence of complicated bio-signals. For therapeutic nanoparticles (NPs), the general lack of effective communication mechanisms with the external cellular environment causes loss of homeostasis, resulting in deprived autonomy, severe macrophage-mediated clearance, and limited tumor accumulation. Here, we develop a multistage signal-interactive system on porous silicon particles through integrating the Self-peptide and Tyr-Ile-Gly-Ser-Arg (YIGSR) peptide into a hierarchical chimeric signaling interface with "don't eat me" and "eat me" signals. This biochemical transceiver can act as both the signal receiver for amantadine to achieve NP transformation and signal conversion as well as the signal source to present different signals sequentially by reversible self-mimicking. Compared with the non-interactive controls, these signal-interactive NPs loaded with AS1411 and tanespimycin (17-AAG) as anticancer drugs improve tumor targeting 2.8-fold and tumor suppression 6.5-fold and showed only 51% accumulation in the liver with restricted hepatic injury.


Asunto(s)
Comunicación Celular/inmunología , Nanopartículas/metabolismo , Neoplasias/inmunología , Humanos , Modelos Moleculares , Estadificación de Neoplasias , Transducción de Señal
10.
Ultrason Sonochem ; 73: 105503, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33662752

RESUMEN

Waste minimization strategy was applied in the current work for synthesis of the catalysts from industrial solid waste, namely desulfurization slag. The starting slag material comprising CaCO3, Ca(OH)2, SiO2, Al2O3, Fe2O3, and TiO2 was processed by various treating agents systematically varying the synthesis parameters. A novel efficient technique - ultrasound irradiation, was applied as an additional synthesis step for intensification of the slag dissolution and crystallization of the new phases. Physico-chemical properties of the starting materials and synthesized catalysts were evaluated by several analytical techniques. Treatment of the industrial slag possessing initially poor crystal morphology and a low surface area (6 m2/g) resulted in formation of highly-crystalline catalysts with well-developed structural properties. Surface area was increased up to 49 m2/g. High basicity of the neat slag as well as materials synthesized on its basis makes possible application of these materials in the reactions requiring basic active sites. Catalytic performance of the synthesized catalysts was elucidated in the synthesis of carbonate esters by carboxymethylation of cinnamyl alcohol with dimethyl carbonate carried out at 150 °C in a batch mode. Ultrasonication of the slag had a positive effect on the catalytic activity. Synthesized catalysts while exhibiting similar selectivity to the desired product (ca. 84%), demonstrated a trend of activity increase for materials prepared using ultrasonication pretreatment. The choice of the treating agent also played an important role in the catalytic performance. The highest selectivity to the desired cinnamyl methyl carbonate (88%) together with the highest activity (TOF35 = 3.89*10-7 (mol/g*s)) was achieved over the material synthesized using 0.6 M NaOH solution as the treating agent with the ultrasound pre-treatment at 80 W for 4 h.

11.
Eur J Pharm Biopharm ; 158: 254-265, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33279602

RESUMEN

Porous silicon (PSi) is a biocompatible and biodegradable material, which can be utilized in biomedical applications. It has several favorable properties, which makes it an excellent material for building engineered nanosystems for drug delivery and diagnostic purposes. One significant hurdle for commercial applications of PSi is the lack of industrial scale production of nanosized PSi particles. Here, we report a novel two-step production method for PSi nanoparticles. The method is based on centrifuge chemical vapor deposition (cCVD) of elemental silicon in an industrial scale reactor followed by electrochemical post-processing to porous particles. Physical properties, biocompatibility and in vivo biodistribution of the cCVD produced nanoparticles were investigated and compared to PSi nanoparticles conventionally produced from silicon wafers by pulse electrochemical etching. Our results demonstrate that the cCVD production provides PSi nanoparticles with comparable physical and biological quality to the conventional method. This method may circumvent several limitations of the conventional method such as the requirements for high purity monocrystalline silicon substrates as starting material and the material losses during the top-down milling process of the pulse-etched films to porous nanoparticles. However, the electroless etching required for the porosification of cCVD-produced nanoparticles limited control over the pore size, but is amenable for scaling of the production to industrial requirements.


Asunto(s)
Portadores de Fármacos/farmacocinética , Composición de Medicamentos/métodos , Nanopartículas/toxicidad , Radiofármacos/administración & dosificación , Silicio/farmacocinética , Animales , Supervivencia Celular/efectos de los fármacos , Centrifugación , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/química , Portadores de Fármacos/toxicidad , Femenino , Radioisótopos de Indio/administración & dosificación , Inyecciones Intravenosas , Ratones , Modelos Animales , Nanopartículas/administración & dosificación , Nanopartículas/química , Porosidad , Células RAW 264.7 , Silicio/administración & dosificación , Silicio/química , Silicio/toxicidad , Distribución Tisular , Pruebas de Toxicidad Aguda
12.
Adv Sci (Weinh) ; 7(15): 2001129, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32775170

RESUMEN

The analysis of nanoparticles' biocompatibility and immunogenicity is mostly performed under a healthy condition. However, more clinically relevant evaluation conducted under pathological condition is less known. Here, the immunogenicity and bio-nano interactions of porous silicon nanoparticles (PSi NPs) are evaluated in an acute liver inflammation mice model. Interestingly, a new mechanism in which PSi NPs can remit the hepatocellular damage and inflammation activation in a surface dependent manner through protein corona formation, which perturbs the inflammation by capturing the pro-inflammatory signaling proteins that are inordinately excreted or exposed under pathological condition, is found. This signal sequestration further attenuates the nuclear factor κB pathway activation and cytokines production from macrophages. Hence, the study proposes a potential mechanism for elucidating the altered immunogenicity of nanomaterials under pathological conditions, which might further offer insights to establish harmonized standards for assessing the biosafety of biomaterials in a disease-specific or personalized manner.

13.
Adv Healthc Mater ; 9(17): e2000529, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32729247

RESUMEN

Biohybrid nanosystems represent the cutting-edge research in biofunctionalization of micro- and nano-systems. Their physicochemical properties bring along advantages in the circulation time, camouflaging from the phagocytes, and novel antigens. This is partially a result of the qualitative differences in the protein corona, and the preferential targeting and uptake in homologous cells. However, the effect of the cell membrane on the cellular endocytosis mechanisms and time has not been fully evaluated yet. Here, the effect is assessed by quantitative flow cytometry analysis on the endocytosis of hydrophilic, negatively charged porous silicon nanoparticles and on their membrane-coated counterparts, in the presence of chemical inhibitors of different uptake pathways. Principal component analysis is used to analyze all the data and extrapolate patterns to highlight the cell-specific differences in the endocytosis mechanisms. Furthermore, the differences in the composition of static protein corona between naked and coated particles are investigated together with how these differences affect the interaction with human macrophages. Overall, the presence of the cell membrane only influences the speed and the entity of nanoparticles association with the cells, while there is no direct effect on the endocytosis pathways, composition of protein corona, or any reduction in macrophage-mediated uptake.


Asunto(s)
Nanopartículas , Corona de Proteínas , Membrana Celular , Endocitosis , Humanos , Porosidad , Silicio
14.
Nucl Med Biol ; 84-85: 102-110, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32334356

RESUMEN

INTRODUCTION: Porous silicon (PSi) nanoparticles are capable of delivering therapeutic payloads providing targeted delivery and sustained release of the payloads. In this work we describe the development and proof-of-concept in vivo evaluation of thermally hydrocarbonized porous silicon (PSi) nanoparticles that are implanted with radioactive 155Tb atoms and coated with red blood cell (RBC) membrane (155Tb-THCPSi). The developed nanocomposites can be utilized as an intravenous delivery platform for theranostic radionuclides. METHODS: THCPSi thin films were implanted with 155Dy ions that decay to 155Tb at the ISOLDE radioactive ion-beam (RIB) facility at CERN. The films were processed to nanoparticles by ball-milling and sonication, and subsequently coated with either a solid lipid and RBC membrane or solely with RBC membrane. The nanocomposites were evaluated in vitro for stability and in vivo for circulation half-life and ex vivo for biodistribution in Balb/c mice. RESULTS: Nanoporous THCPSi films were successfully implanted with 155Tb and processed to coated nanoparticles. The in vitro stability of the particles in plasma and buffer solutions was not significantly different between the particle types, and therefore the RBC membrane coated particles with less laborious processing method were chosen for the biological evaluation. The RBC membrane coating enhanced significantly the blood half-life compared to bare THCPSi particles. In the ex vivo biodistribution study a pronounced accumulation to the spleen was found, with lower uptake in the liver and a minor uptake in the lung, gall bladder and bone marrow. CONCLUSIONS: We have demonstrated, using 155Tb RIB-implanted PSi nanoparticles coated with mouse RBC membranes, the feasibility of using such a theranostic nanosystem for the delivery of RIB based radionuclides with prolonged circulation time. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: For the first time, the RIB implantation technique has been utilized to produce PSi nanoparticle with a surface modified for better persistence in circulation. When optimized, these particles could be used in targeted radionuclide therapy with a combination of chemotherapeutic payload within the PSi structure.


Asunto(s)
Membrana Eritrocítica/química , Nanopartículas/química , Radioisótopos/química , Silicio/química , Terbio/química , Animales , Tampones (Química) , Estabilidad de Medicamentos , Semivida , Humanos , Ratones , Porosidad
15.
ACS Appl Mater Interfaces ; 12(6): 6899-6909, 2020 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-31967771

RESUMEN

Heart tissue engineering is critical in the treatment of myocardial infarction, which may benefit from drug-releasing smart materials. In this study, we load a small molecule (3i-1000) in new biodegradable and conductive patches for application in infarcted myocardium. The composite patches consist of a biocompatible elastomer, poly(glycerol sebacate) (PGS), coupled with collagen type I, used to promote cell attachment. In addition, polypyrrole is incorporated because of its electrical conductivity and to induce cell signaling. Results from the in vitro experiments indicate a high density of cardiac myoblast cells attached on the patches, which stay viable for at least 1 month. The degradation of the patches does not show any cytotoxic effect, while 3i-1000 delivery induces cell proliferation. Conductive patches show high blood wettability and drug release, correlating with the rate of degradation of the PGS matrix. Together with the electrical conductivity and elongation characteristics, the developed biomaterial fits the mechanical, conductive, and biological demands required for cardiac treatment.


Asunto(s)
Decanoatos/química , Sistemas de Liberación de Medicamentos/métodos , Glicerol/análogos & derivados , Infarto del Miocardio/tratamiento farmacológico , Polímeros/química , Bibliotecas de Moléculas Pequeñas/química , Animales , Sistemas de Liberación de Medicamentos/instrumentación , Conductividad Eléctrica , Glicerol/química , Humanos , Ensayo de Materiales , Ratones , Miocitos Cardíacos/citología , Miocitos Cardíacos/efectos de los fármacos , Nanopartículas/química , Pirroles/química , Bibliotecas de Moléculas Pequeñas/farmacología
16.
RSC Adv ; 10(58): 35198-35205, 2020 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-35515680

RESUMEN

Erythrocyte-based drug delivery systems have been investigated for their biocompatibility, long circulation time, and capability to transport cargo all around the body, thus presenting enormous potential in medical applications. In this study, we investigated hybrid nanoparticles consisting of nano-sized autologous or allogeneic red blood cell (RBC) membranes encapsulating porous silicon nanoparticles (PSi NPs). These NPs were functionalized with a model cancer antigen TRP2, which was either expressed on the surface of the RBCs by a cell membrane-mimicking block copolymer polydimethylsiloxane-b-poly-2-methyl-2-oxazoline, or attached on the PSi NPs, thus hidden within the encapsulation. When in the presence of peripheral blood immune cells, these NPs resulted in apoptotic cell death of T cells, where the NPs having TRP2 within the encapsulation led to a stronger T cell deletion. The deletion of the T cells did not change the relative proportion of CD4+ and cytotoxic CD8+ T cells. Overall, this work shows the combination of nano-sized RBCs, PSi, and antigenic peptides may have use in the treatment of autoimmune diseases.

17.
Biomaterials ; 227: 119556, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31670035

RESUMEN

Generation of new neurons by utilizing the regenerative potential of adult neural stem cells (NSCs) and neuroblasts is an emerging therapeutic strategy to treat various neurodegenerative diseases, including neuronal loss after stroke. Committed to neuronal lineages, neuroblasts are differentiated from NSCs and have a lower proliferation rate. In stroke the proliferation of the neuroblasts in the neurogenic areas is increased, but the limiting factor for regeneration is the poor survival of migrating neuroblasts. Survival of neuroblasts can be promoted by small molecules; however, new drug delivery methods are needed to specifically target these cells. Herein, to achieve specific targeting, we have engineered biofunctionalized porous silicon nanoparticles (PSi NPs) conjugated with a specific antibody against polysialylated neural cell adhesion molecule (PSA-NCAM). The PSi NPs loaded with a small molecule drug, SC-79, were able to increase the activity of the Akt signaling pathway in doublecortin positive neuroblasts both in cultured cells and in vivo in the rat brain. This study opens up new possibilities to target drug effects to migrating neuroblasts and facilitate differentiation, maturation and survival of developing neurons. The conjugated PSi NPs are a novel tool for future studies to develop new therapeutic strategies aiming at regenerating functional neurocircuitry after stoke.


Asunto(s)
Nanopartículas , Células-Madre Neurales , Accidente Cerebrovascular , Animales , Proteína Doblecortina , Porosidad , Ratas , Silicio , Accidente Cerebrovascular/tratamiento farmacológico
18.
ACS Nano ; 13(11): 13056-13064, 2019 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-31670505

RESUMEN

Hierarchically nanostructured silicon was produced by regenerative electroless etching (ReEtching) of Si powder made from pulverized anodized porous silicon. This material is characterized by ∼15 nm mesopores, into the walls of which tortuous 2-4 nm pores have been introduced. The walls are sufficiently narrow that they support quantum-confined crystallites that are photoluminescent. With suitable parameters, the ReEtching process also provides control over the emission color of the photoluminescence. Ball milling and hydrosilylation of this powder with undecylenic acid produces nanoparticles with hydrodynamic diameter of ∼220 nm that exhibit robust and bright luminescence that can be excited with either one ultraviolet/visible photon or two near-infrared photons. The long-lived, robust visible photoluminescence of these chemically passivated porous silicon nanoparticles is well-suited for bioimaging and theranostic applications.

19.
Nanomaterials (Basel) ; 9(6)2019 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-31159254

RESUMEN

Memristors are two terminal electronic components whose conductance depends on the amount of charge that has flown across them over time. This dependence can be gradual, such as in synaptic memristors, or abrupt, as in resistive switching memristors. Either of these memory effects are very promising for the development of a whole new generation of electronic devices. For the successful implementation of practical memristors, however, the development of low cost industry compatible memristive materials is required. Here the memristive properties of differently processed porous silicon structures are presented, which are suitable for different applications. Electrical characterization and SPICE simulations show that laser-carbonized porous silicon shows a strong synaptic memristive behavior influenced by defect diffusion, while wet-oxidized porous silicon has strong resistance switching properties, with switching ratios over 8000. Results show that practical memristors of either type can be achieved with porous silicon whose memristive properties can be adjusted by the proper material processing. Thus, porous silicon may play an important role for the successful realization of practical memristorics with cost-effective materials and processes.

20.
ACS Nano ; 13(6): 6477-6490, 2019 06 25.
Artículo en Inglés | MEDLINE | ID: mdl-31100004

RESUMEN

Recent approaches in the treatment of cancer focus on involving the immune system to control the tumor growth. The administration of immunotherapies, like checkpoint inhibitors, has shown impressive results in the long term survival of patients. Cancer vaccines are being investigated as further tools to prime tumor-specific immunity. Biomaterials show potential as adjuvants in the formulation of vaccines, and biomimetic elements derived from the membrane of tumor cells may widen the range of antigens contained in the vaccine. Here, we show how mice presenting an aggressive melanoma tumor model treated twice with the complete nanovaccine formulation showed control on the tumor progression, while in a less aggressive model, the animals showed remission and control on the tumor progression, with a modification in the immunological profile of the tumor microenvironment. We also prove that co-administration of the nanovaccine together with a checkpoint inhibitor increases the efficacy of the treatment (87.5% of the animals responding, with 2 remissions) compared to the checkpoint inhibitor alone in the B16.OVA model. Our platform thereby shows potential applications as a cancer nanovaccine in combination with the standard clinical care treatment for melanoma cancers.


Asunto(s)
Vacunas contra el Cáncer/inmunología , Melanoma/terapia , Nanopartículas/química , Animales , Células Presentadoras de Antígenos/inmunología , Antígenos de Neoplasias/inmunología , Vacunas contra el Cáncer/administración & dosificación , Vacunas contra el Cáncer/uso terapéutico , Línea Celular Tumoral , Membrana Celular/química , Ratones , Ratones Endogámicos C57BL , Microfluídica/métodos , Microambiente Tumoral/inmunología
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