Publications by authors named "Victor Sebastian"

85 Publications

Nanogels with High Loading of Anesthetic Nanocrystals for Extended Duration of Sciatic Nerve Block.

ACS Appl Mater Interfaces 2021 Apr 6;13(15):17220-17235. Epub 2021 Apr 6.

Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de Zaragoza, Zaragoza 50009, Spain.

The development of thermoresponsive nanogels loaded with nanocrystals of the local anesthetic bupivacaine nanocrystals (BNCs) for prolonged peripheral nerve pain relief is reported here. BNCs were prepared using the antisolvent precipitation method from the hydrophobic form of bupivacaine (bupivacaine free base). The as-prepared BNCs were used stand-alone or encapsulated in temperature-responsive poly(ethylene glycol) methyl ether methacrylate (OEGMA)-based nanogels, resulting in bupivacaine NC-loaded nanogels (BNC-nanogels) of monodisperse size. The synthesis protocol has rendered high drug loadings (., 93.8 ± 1.5 and 84.8 ± 1.2 wt % for the NC and BNC-nanogels, respectively) and fast drug dissolution kinetics in the resulting composite material. tests demonstrated the efficacy of the formulation along with an extended duration of sciatic nerve block in murine models of more than 8 h with a formulation containing only 2 mg of the local anesthetic thanks to the thermoresponsive character of the polymer, which, at body temperature, becomes hydrophobic and acts as a diffusion barrier for the encapsulated drug nanocrystals. The hydrophobicity of the encapsulated bupivacaine free base probably facilitates its pass through cell membranes and also binds strongly to their hydrophobic lipid bilayer, thereby protecting molecules from diffusion to extracellular media and to the bloodstream, reducing their clearance. When using BNC-nanogels, the duration of the anesthetic blockage lasted twice as long as compared to the effect of just BNCs or a conventional bupivacaine hydrochloride solution both containing equivalent amounts of the free drug. Results of the tests showed enough sensory nerve block to potentially relieve pain, but still having mobility in the limb, which enables motor function when required. The BNC-nanogels presented minimal toxicity in the study due to their sustained drug release and excellent biocompatibility. The encapsulation of nano-sized crystals of bupivacaine provides a prolonged regional anesthesia with reduced toxicity, which could be advantageous in the management of chronic pain.
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http://dx.doi.org/10.1021/acsami.1c00894DOI Listing
April 2021

Supramolecular Functionalizable Linear-Dendritic Block Copolymers for the Preparation of Nanocarriers by Microfluidics.

Polymers (Basel) 2021 Feb 25;13(5). Epub 2021 Feb 25.

Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de Zaragoza, 50009 Zaragoza, Spain.

Hybrid linear-dendritic block copolymers (LDBCs) having dendrons with a precise number of peripheral groups that are able to supramolecular bind functional moieties are challenging materials as versatile polymeric platforms for the preparation of functional polymeric nanocarriers. LDBCs that are based on polyethylene glycol (PEG) as hydrophilic blocks and dendrons derived from bis-MPA having 2,6-diacylaminopyridine (DAP) units have been efficiently synthesized by the click coupling of preformed blocks, as was demonstrated by spectroscopic techniques and mass spectrometry. Self-assembly ability was first checked by nanoprecipitation. A reproducible and fast synthesis of aggregates was accomplished by microfluidics optimizing the total flow rate and phase ratio to achieve spherical micelles and/or vesicles depending on dendron generation and experimental parameters. The morphology and size of the self-assemblies were studied by TEM, Cryogenic Transmission Electron Microscopy (cryo-TEM), and Dynamic Light Scattering (DLS). The cytotoxicity of aggregates synthesized by microfluidics and the influence on apoptosis and cell cycle evaluation was studied on four cell lines. The self-assemblies are not cytotoxic at doses below 0.4 mg mL. Supramolecular functionalization using thymine derivatives was explored for reversibly cross-linking the hydrophobic blocks. The results open new possibilities for their use as drug nanocarriers with a dynamic cross-linking to improve nanocarrier stability but without hindering disassembly to release molecular cargoes.
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http://dx.doi.org/10.3390/polym13050684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956801PMC
February 2021

Key Population Hotspots in Nigeria for Targeted HIV Program Planning: Mapping, Validation, and Reconciliation.

JMIR Public Health Surveill 2021 Feb 22;7(2):e25623. Epub 2021 Feb 22.

Division of Global HIV & TB, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, GA, United States.

Background: With the fourth highest HIV burden globally, Nigeria is characterized as having a mixed HIV epidemic with high HIV prevalence among key populations, including female sex workers, men who have sex with men, and people who inject drugs. Reliable and accurate mapping of key population hotspots is necessary for strategic placement of services and allocation of limited resources for targeted interventions.

Objective: We aimed to map and develop a profile for the hotspots of female sex workers, men who have sex with men, and people who inject drugs in 7 states of Nigeria to inform HIV prevention and service programs and in preparation for a multiple-source capture-recapture population size estimation effort.

Methods: In August 2018, 261 trained data collectors from 36 key population-led community-based organizations mapped, validated, and profiled hotspots identified during the formative assessment in 7 priority states in Nigeria designated by the United States President's Emergency Plan for AIDS Relief. Hotspots were defined as physical venues wherein key population members frequent to socialize, seek clients, or engage in key population-defining behaviors. Hotspots were visited by data collectors, and each hotspot's name, local government area, address, type, geographic coordinates, peak times of activity, and estimated number of key population members was recorded. The number of key population hotspots per local government area was tabulated from the final list of hotspots.

Results: A total of 13,899 key population hotspots were identified and mapped in the 7 states, that is, 1297 in Akwa Ibom, 1714 in Benue, 2666 in Cross River, 2974 in Lagos, 1550 in Nasarawa, 2494 in Rivers, and 1204 in Federal Capital Territory. The most common hotspots were those frequented by female sex workers (9593/13,899, 69.0%), followed by people who inject drugs (2729/13,899, 19.6%) and men who have sex with men (1577/13,899, 11.3%). Although hotspots were identified in all local government areas visited, more hotspots were found in metropolitan local government areas and state capitals.

Conclusions: The number of key population hotspots identified in this study is more than that previously reported in similar studies in Nigeria. Close collaboration with key population-led community-based organizations facilitated identification of many new and previously undocumented key population hotspots in the 7 states. The smaller number of hotspots of men who have sex with men than that of female sex workers and that of people who inject drugs may reflect the social pressure and stigma faced by this population since the enforcement of the 2014 Same Sex Marriage (Prohibition) Act, which prohibits engaging in intimate same-sex relationships, organizing meetings of gays, or patronizing gay businesses.
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http://dx.doi.org/10.2196/25623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939933PMC
February 2021

The extent of protein hydration dictates the preference for heterogeneous or homogeneous nucleation generating either parallel or antiparallel β-sheet α-synuclein aggregates.

Chem Sci 2020 Nov 15;11(43):11902-11914. Epub 2020 Oct 15.

Biocomputation and Complex Systems Physics Institute (BIFI)-Joint Unit BIFI-IQFR (CSIC) , University of Zaragoza , 50018 Zaragoza , Spain . Email:

α-Synuclein amyloid self-assembly is the hallmark of a number of neurodegenerative disorders, including Parkinson's disease, although there is still very limited understanding about the factors and mechanisms that trigger this process. Primary nucleation has been observed to be initiated at hydrophobic/hydrophilic interfaces by heterogeneous nucleation generating parallel β-sheet aggregates, although no such interfaces have yet been identified . In this work, we have discovered that α-synuclein can self-assemble into amyloid aggregates by homogeneous nucleation, without the need of an active surface, and with a preference for an antiparallel β-sheet arrangement. This particular structure has been previously proposed to be distinctive of stable toxic oligomers and we here demonstrate that it indeed represents the most stable structure of the preferred amyloid pathway triggered by homogeneous nucleation under limited hydration conditions, including those encountered inside α-synuclein droplets generated by liquid-liquid phase separation. In addition, our results highlight the key role that water plays not only in modulating the transition free energy of amyloid nucleation, and thus governing the initiation of the process, but also in dictating the type of preferred primary nucleation and the type of amyloid polymorph generated depending on the extent of protein hydration. These findings are particularly relevant in the context of α-synuclein aggregation where the protein can encounter a variety of hydration conditions in different cellular microenvironments, including the vicinity of lipid membranes or the interior of membraneless compartments, which could lead to the formation of remarkably different amyloid polymorphs by either heterogeneous or homogeneous nucleation.
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http://dx.doi.org/10.1039/d0sc05297cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816767PMC
November 2020

Nondestructive production of exosomes loaded with ultrathin palladium nanosheets for targeted bio-orthogonal catalysis.

Nat Protoc 2021 01 27;16(1):131-163. Epub 2020 Nov 27.

Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de Zaragoza, Zaragoza, Spain.

The use of exosomes as selective delivery vehicles of therapeutic agents, such as drugs or hyperthermia-capable nanoparticles, is being intensely investigated on account of their preferential tropism toward their parental cells. However, the methods used to introduce a therapeutic load inside exosomes often involve disruption of their membrane, which may jeopardize their targeting capabilities, attributed to their surface integrins. On the other hand, in recent years bio-orthogonal catalysis has emerged as a new tool with a myriad of potential applications in medicine. These bio-orthogonal processes, often based on Pd-catalyzed chemistry, would benefit from systems capable of delivering the catalyst to target cells. It is therefore highly attractive to combine the targeting capabilities of exosomes and the bio-orthogonal potential of Pd nanoparticles to create new therapeutic vectors. In this protocol, we provide detailed information on an efficient procedure to achieve a high load of catalytically active Pd nanosheets inside exosomes, without disrupting their membranes. The protocol involves a multistage process in which exosomes are first harvested, subjected to impregnation with a Pd salt precursor followed by a mild reduction process using gas-phase CO, which acts as both a reducing and growth-directing agent to produce the desired nanosheets. The technology is scalable, and the protocol can be conducted by any researcher having basic biology and chemistry skills in ~3 d.
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http://dx.doi.org/10.1038/s41596-020-00406-zDOI Listing
January 2021

Covalent Cross-Linking of 2H-MoS Nanosheets.

Chemistry 2021 Feb 12;27(9):2993-2996. Epub 2021 Jan 12.

IMDEA Nanociencia, C/Faraday 9 Ciudad Universitaria de Cantoblanco, 28049, Madrid, Spain.

The combination of 2D materials opens a wide range of possibilities to create new-generation structures with multiple applications. Covalently cross-linked approaches are a ground-breaking strategy for the formation of homo or heterostructures made by design. However, the covalent assembly of transition metal dichalcogenides flakes is relatively underexplored. Here, a simple covalent cross-linking method to build 2H-MoS -MoS homostructures is described, using commercially available bismaleimides. These assemblies are mainly connected vertically, basal plane to basal plane, creating specific molecular sized spaces between MoS sheets. Therefore, this straightforward approach gives access to the controlled connection of sulfide-based 2D materials.
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http://dx.doi.org/10.1002/chem.202004366DOI Listing
February 2021

Towards plant-mediated chemistry - Au nanoparticles obtained using aqueous extract of Rosa damascena and their biological activity in vitro.

J Inorg Biochem 2021 Jan 2;214:111300. Epub 2020 Nov 2.

Department of Biochemistry, Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski Krakow University, Gustawa Herlinga-Grudzińskiego 1, 30-705 Kraków, Poland. Electronic address:

An eco-friendly, efficient, and controlled synthesis of gold nanoparticles with application of the aqueous extract of Rosa damascena (Au@RD NPs) without using any other reducing agents was studied. Au@RD NPs of narrow size distribution were characterized by UV-vis and FT-IR spectroscopies, transmission electron microscopy, X-ray powder diffraction, X-ray photoelectron spectroscopy, particle size analysis, and zeta potential measurements. In vitro stability experiments revealed that the Au@RD NPs were stable for over a year (pH ~ 3.5), proving a significant stabilizing potential of the aqueous RD extract. The high total content of polyphenols, flavonoids, and reducing sugars along with the powerful antioxidant activity of the RD extract was determined by spectroscopic and analytical methods. Colloids prepared from the purified and lyophilized Au@RD NPs (electrokinetic potential of ca. -33 mV) were stable for at least 24 h under terms similar to physiological conditions (pH = 7.4, PBS). The in vitro cytotoxicity of Au@RD NPs was investigated against peripheral blood mononuclear lymphocytes (PBML), acute promyelocytic leukemia (HL60), and human lung adenocarcinoma (A549). Selective cytotoxicity of Au@RD NPs towards cancer cells (HL60, A549) over normal cells (PBML) in vitro was explicitly demonstrated by viability assays. Comet assay revealed a higher level of DNA damages in cancer cells when compared with normal ones. Apoptotic death in cancer cells was proved by measuring caspases activity. Thus, the developed Au@RD NPs, obtained by the plant-mediated green synthesis, are attractive hybrid materials for the medical applications combining two active components - metal nanoparticles platform and plant-derived metabolites.
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http://dx.doi.org/10.1016/j.jinorgbio.2020.111300DOI Listing
January 2021

Isolation of exosomes from whole blood by a new microfluidic device: proof of concept application in the diagnosis and monitoring of pancreatic cancer.

J Nanobiotechnology 2020 Oct 22;18(1):150. Epub 2020 Oct 22.

Department of Chemical Engineering, University of Zaragoza, 50018, Zaragoza, Spain.

Background: Exosomes are endocytic-extracellular vesicles with a diameter around 100 nm that play an essential role on the communication between cells. In fact, they have been proposed as candidates for the diagnosis and the monitoring of different pathologies (such as Parkinson, Alzheimer, diabetes, cardiac damage, infection diseases or cancer).

Results: In this study, magnetic nanoparticles (FeONPs) were successfully functionalized with an exosome-binding antibody (anti-CD9) to mediate the magnetic capture in a microdevice. This was carried out under flow in a 1.6 mm (outer diameter) microchannel whose wall was in contact with a set of NdFeB permanent magnets, giving a high magnetic field across the channel diameter that allowed exosome separation with a high yield. To show the usefulness of the method, the direct capture of exosomes from whole blood of patients with pancreatic cancer (PC) was performed, as a proof of concept. The captured exosomes were then subjected to analysis of CA19-9, a protein often used to monitor PC patients.

Conclusions: Here, we describe a new microfluidic device and the procedure for the isolation of exosomes from whole blood, without any need of previous isolation steps, thereby facilitating translation to the clinic. The results show that, for the cases analyzed, the evaluation of CA19-9 in exosomes was highly sensitive, compared to serum samples.
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http://dx.doi.org/10.1186/s12951-020-00701-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579907PMC
October 2020

Continuous Single-Phase Synthesis of [Au(Cys)] Nanoclusters and their Photobactericidal Enhancement.

ACS Appl Mater Interfaces 2020 Oct 19;12(43):49021-49029. Epub 2020 Oct 19.

Materials Chemistry Research Centre, Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, United Kingdom.

Thiolate-gold nanoclusters have various applications. However, most of the synthesis methods require prolonged synthesis times from several hours to days. In the present study, we report a rapid synthesis method for [Au(Cys)] nanoclusters and their application for photobactericidal enhancement. For [Au(Cys)] synthesis, we employed a tube-in-tube membrane reactor using CO as a reducing agent at elevated temperatures. This approach allows continuous generation of high-quality [Au(Cys)] within 3 min. Photobactericidal tests against showed that crystal violet-treated polymer did not have photobactericidal activity, but addition of [Au(Cys)] in the treated polymer demonstrated a potent photobactericidal activity at a low white light flux, resulting in >4.29 log reduction in viable bacteria numbers. Steady-state and time-resolved photoluminescence spectroscopies demonstrated that after light irradiation, photoexcited electrons in crystal violet flowed to [Au(Cys)] in the silicone, suggesting that redox reaction from [Au(Cys)] enhanced the photobactericidal activity. Stability tests revealed that leaching of crystal violet and [Au(Cys)] from the treated silicone was negligible and cyclic testing showed that the silicone maintained a strong photobactericidal activity after repeated use.
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http://dx.doi.org/10.1021/acsami.0c07691DOI Listing
October 2020

Bioorthogonal Uncaging of Cytotoxic Paclitaxel through Pd Nanosheet-Hydrogel Frameworks.

J Med Chem 2020 09 17;63(17):9650-9659. Epub 2020 Aug 17.

Cancer Cancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XR, U.K.

The promising potential of bioorthogonal catalysis in biomedicine is inspiring incremental efforts to design strategies that regulate drug activity in living systems. To achieve this, it is not only essential to develop customized inactive prodrugs and biocompatible metal catalysts but also the right physical environment for them to interact and enable drug production under spatial and/or temporal control. Toward this goal, here, we report the first inactive precursor of the potent broad-spectrum anticancer drug paclitaxel (a.k.a. Taxol) that is stable in cell culture and labile to Pd catalysts. This new prodrug is effectively uncaged in cancer cell culture by Pd nanosheets captured within agarose and alginate hydrogels, providing a biodegradable catalytic framework to achieve controlled release of one of the most important chemotherapy drugs in medical practice. The compatibility of bioorthogonal catalysis and physical hydrogels opens up new opportunities to administer and modulate the mobility of transition metal catalysts in living environs.
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http://dx.doi.org/10.1021/acs.jmedchem.0c00781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497487PMC
September 2020

Controlling Particle Size and Release Kinetics in the Sustained Delivery of Oral Antibiotics Using pH-Independent Mucoadhesive Polymers.

Mol Pharm 2020 09 5;17(9):3314-3327. Epub 2020 Aug 5.

Department of Chemical Engineering, Aragon Institute of Nanoscience (INA), University of Zaragoza, Aragón Materials Science Institute, ICMA, Campus Río Ebro-Edificio I+D, C/ Poeta Mariano Esquillor S/N, 50018 Zaragoza, Spain.

Copolymers synthesized from acrylic acid and methacrylic acid used as gastroprotective and mucoadhesive enteric coatings have been used to prepare micro- (∼2 μm), submicro- (∼200 nm), and nanoparticles (∼20 nm) containing rifampicin (Rif) to obtain time-controlled drug release kinetics. Different particle sizes and drug release kinetics have been obtained using different synthesis conditions and fabrication techniques including the use of an electrosprayer and an interdigital microfabricated micromixer. The antimicrobial action of the encapsulated Rif has been demonstrated against ATCC 25923 and compared with the effect of the equivalent dose of the free macrolide antibiotic. At low concentrations, the encapsulated antibiotic showed superior antimicrobial activity than the free drug. The stability of the developed particles has been evaluated under simulated gastric and intestinal conditions. At the concentrations tested, a reduced cytotoxicity against different human cell lines was observed after analyzing their subcytotoxic doses and the influence on their cell cycle by flow cytometry. Drug release kinetics can be tuned by adjusting particle sizes, and it would be possible to reach the minimum inhibitory concentration or the minimum bactericidal concentration at different time points depending on the medical needs.
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http://dx.doi.org/10.1021/acs.molpharmaceut.0c00408DOI Listing
September 2020

Microflow Nanoprecipitation of Positively Charged Gastroresistant Polymer Nanoparticles of Eudragit RS100: A Study of Fluid Dynamics and Chemical Parameters.

Materials (Basel) 2020 Jun 30;13(13). Epub 2020 Jun 30.

Department of Chemical Engineering and Environmental Technology, Aragon Institute of Nanoscience (INA), Instituto de Ciencia de Materiales de Aragon-ICMA, University of Zaragoza, 50018 Zaragoza, Spain.

The objective of the present work was to produce gastroresistant Eudragit RS100 nanoparticles by a reproducible synthesis approach that ensured mono-disperse nanoparticles under the size of 100 nm. Batch and micromixing nanoprecipitation approaches were selected to produce the demanded nanoparticles, identifying the critical parameters affecting the synthesis process. To shed some light on the formulation of the targeted nanoparticles, the effects of particle size and homogeneity of fluid dynamics, and physicochemical parameters such as polymer concentration, type of solvent, ratio of solvent to antisolvent, and total flow rate were studied. The physicochemical characteristics of resulting nanoparticles were studied applying dynamic light scattering (DLS) particle size analysis and electron microscopy imaging. Nanoparticles produced using a micromixer demonstrated a narrower and more homogenous distribution than the ones obtained under similar conditions in conventional batch reactors. Besides, fluid dynamics ensured that the best mixing conditions were achieved at the highest flow rate. It was concluded that nucleation and growth events must also be considered to avoid uncontrolled nanoparticle growth and evolution at the collection vial. Further, rifampicin-encapsulated nanoparticles were prepared using both approaches, demonstrating that the micromixing-assisted approach provided an excellent control of the particle size and polydispersity index. Not only the micromixing-assisted nanoprecipitation promoted a remarkable control in the nanoparticle formulation, but also it enhanced drug encapsulation efficiency and loading, as well as productivity. To the best of our knowledge, this was the very first time that drug-loaded Eudragit RS100 nanoparticles (NPs) were produced in a continuous fashion under 100 nm (16.5 ± 4.3 nm) using microreactor technology. Furthermore, we performed a detailed analysis of the influence of various fluid dynamics and physicochemical parameters on the size and uniformity of the resulting nanoparticles. According to these findings, the proposed methodology can be a useful approach to synthesize a myriad of nanoparticles of alternative polymers.
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http://dx.doi.org/10.3390/ma13132925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372341PMC
June 2020

Novel intracellular antibiotic delivery system against : cloxacillin-loaded poly(d,l-lactide-co-glycolide) acid nanoparticles.

Nanomedicine (Lond) 2020 05 6;15(12):1189-1203. Epub 2020 May 6.

Microbiology Department, Hospital Universitari Germans Trias i Pujol, Fundació Institut d'Investigació en Ciències de la Salut GermansTrias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.

First, to compare minimum inhibitory concentrations (MIC) of free cloxacillin and cloxacillin-containing nanoparticles (NP) against methicillin-susceptible (MSSA) and resistant (MRSA) and second, to assess NP antimicrobial activity against intracellular . Poly(d,l-lactide-co-glycolide) acid (PLGA)-NP were loaded with cloxacillin and physico-chemically characterized. MICs were determined for reference strains Newman-(MSSA) and USA300-(MRSA). Murine alveolar macrophages were infected, and bacterial intracellular survival was assessed after incubating with free-cloxacillin or PLGA-cloxacillin-NP. For both isolates, MICs for antibiotic-loaded-NP were lower than those obtained with free cloxacillin, indicating that the drug encapsulation improves antimicrobial activity. A sustained antibiotic release was demonstrated when using the PLGA-cloxacillin-NP. When considering the lowest concentrations, the use of drug-loaded NP enabled a higher reduction of intracellular bacterial load.
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http://dx.doi.org/10.2217/nnm-2019-0371DOI Listing
May 2020

Customized hybrid and NIR-light triggered thermoresponsive drug delivery microparticles synthetized by photopolymerization in a one-step flow focusing continuous microreactor.

Colloids Surf B Biointerfaces 2020 Jun 25;190:110904. Epub 2020 Feb 25.

Department of Chemical Engineering. Aragon Institute of Nanoscience (INA) and Instituto de Ciencia de Materiales de Aragón (ICMA), Universidad de Zaragoza-CSIC, University of Zaragoza, Campus Río Ebro-Edificio I+D, C/ Poeta Mariano Esquillor S/N, 50018, Zaragoza, Spain; Aragon Health Research Institute (IIS Aragón), 50009, Zaragoza, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN, 28029, Madrid, Spain.

Photopolymerization is a selective technique that takes advantage of light-sensitive molecules to initiate and propagate monomeric structures to render covalently bonded macromolecular materials structures known as polymers. Herein, we present a novel one-step microfluidic synthesis of customized hybrid-thermoresponsive Poly(N-isopropylacrylamide) (PNIPAm) based microparticles (MPs) containing plasmonic hollow gold nanoparticles (HGNPs) and bupivacaine (BVP) used as a model drug. Those hybrid microparticles were prepared using a flow-focusing microreactor coupled to a UV LED device built with a simple outer PTFE tubing and an inner flexible capillary. Different tubing characteristics and flow rate ratios were altered in order to control the size of the resulting microparticles. In addition, components such as monomer, crosslinker and photoinitiator concentrations, as well as LED intensity and irradiation time were tuned to obtain different MPs and their characteristics and polymerization rates were compared by Gel Permeation Chromatography (GPC). Thermoresponsive properties were analyzed and the presence of HGNPs was confirmed in light-activated triggered drug release applications. Bupivacaine loading and release studies were evaluated with the resulting hollow and solid microparticles (which were obtained depending on the polymerization rate used) and their temperature responsiveness was assessed using a NIR laser when HGNPs were present in the constructs. Finally, cytotoxicity studies, cell-cycle arrest and apoptotic induction were carried out to certify their suitability for further biomedical applications to be used as triggerable drug depots.
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http://dx.doi.org/10.1016/j.colsurfb.2020.110904DOI Listing
June 2020

Photocatalytic and antimicrobial multifunctional nanocomposite membranes for emerging pollutants water treatment applications.

Chemosphere 2020 Jul 21;250:126299. Epub 2020 Feb 21.

BCMaterials, Parque Científico y Tecnológico de Bizkaia, 48160, Derio, Spain; IKERBASQUE, Basque Foundation for Science, 48013, Bilbao, Spain. Electronic address:

Emerging pollutants represent a new global problem for water quality. As these compounds get into the environment, they cause severe threats to aquatic environments and human health and are typically resistant to conventional wastewater treatments. In this work, TiO nanoparticles surface was functionalized with silver (Ag) nanoparticles, and solvent cast and electrospun membranes of poly (vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) were prepared with different concentrations of TiO and Ag-TiO to produce a multifunctional material. The photocatalytic activity of the nanocomposites was evaluated through the degradation of norfloxacin under ultraviolet (UV) and visible radiation. It is shown that nanocomposites with Ag-TiO show the highest degradation efficiencies: 64.2% under UV and 80.7% under visible radiation, for 90 and 300 min, respectively. Furthermore, the recyclability of the membranes has also been demonstrated. Finally, it is shown the antimicrobial activity of the nanocomposite membranes, demonstrating the suitability of the Ag-TiO/PVDF-HFP nanocomposites as multifunctional photocatalytic and antimicrobial membranes for water remediation applications.
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http://dx.doi.org/10.1016/j.chemosphere.2020.126299DOI Listing
July 2020

Controlled Covalent Functionalization of 2 H-MoS with Molecular or Polymeric Adlayers.

Chemistry 2020 May 31;26(29):6629-6634. Epub 2020 Mar 31.

IMDEA Nanociencia, Ciudad Universitaria de Cantoblanco, C/Faraday 9, 28049, Madrid, Spain.

Most air-stable 2D materials are relatively inert, which makes their chemical modification difficult. In particular, in the case of MoS , the semiconducting 2 H-MoS is much less reactive than its metallic counterpart, 1T-MoS . As a consequence, there are hardly any reliable methods for the covalent modification of 2 H-MoS . An ideal method for the chemical functionalization of such materials should be both mild, not requiring the introduction of a large number of defects, and versatile, allowing for the decoration with as many different functional groups as possible. Herein, a comprehensive study on the covalent functionalization of 2 H-MoS with maleimides is presented. The use of a base (Et N) leads to the in situ formation of a succinimide polymer layer, covalently connected to MoS . In contrast, in the absence of base, functionalization stops at the molecular level. Moreover, the functionalization protocol is mild (occurs at room temperature), fast (nearly complete in 1 h), and very flexible (11 different solvents and 10 different maleimides tested). In practical terms, the procedures described here allow for the chemist to manipulate 2 H-MoS in a very flexible way, decorating it with polymers or molecules, and with a wide range of functional groups for subsequent modification. Conceptually, the spurious formation of an organic polymer might be general to other methods of functionalization of 2D materials, where a large excess of molecular reagents is typically used.
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http://dx.doi.org/10.1002/chem.202000068DOI Listing
May 2020

Extracellular Vesicles-Based Biomarkers Represent a Promising Liquid Biopsy in Endometrial Cancer.

Cancers (Basel) 2019 Dec 12;11(12). Epub 2019 Dec 12.

Translational Medical Oncology Group (Oncomet), Health Research Institute of Santiago de Compostela (IDIS), University Hospital of Santiago de Compostela (SERGAS), Trav. Choupana s/n, 15706 Santiago de Compostela, Spain.

Tumor-derived extracellular vesicles (EVs) are secreted in large amounts into biological fluids of cancer patients. The analysis of EVs cargoes has been associated with patient´s outcome and response to therapy. However, current technologies for EVs isolation are tedious and low cost-efficient for routine clinical implementation. To explore the clinical value of circulating EVs analysis we attempted a proof-of-concept in endometrial cancer (EC) with ExoGAG, an easy to use and highly efficient new technology to enrich EVs. Technical performance was first evaluated using EVs secreted by Hec1A cells. Then, the clinical value of this strategy was questioned by analyzing the levels of two well-known tissue biomarkers in EC, L1 cell adhesion molecule (L1CAM) and Annexin A2 (ANXA2), in EVs purified from plasma in a cohort of 41 EC patients and 20 healthy controls. The results demonstrated the specific content of ANXA2 in the purified EVs fraction, with an accurate sensitivity and specificity for EC diagnosis. Importantly, high ANXA2 levels in circulating EVs were associated with high risk of recurrence and non-endometrioid histology suggesting a potential value as a prognostic biomarker in EC. These results also confirmed ExoGAG technology as a robust technique for the clinical implementation of circulating EVs analyses.
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http://dx.doi.org/10.3390/cancers11122000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966595PMC
December 2019

Triggered drug release from hybrid thermoresponsive nanoparticles using near infrared light.

Nanomedicine (Lond) 2020 02 27;15(3):219-234. Epub 2019 Nov 27.

Department of Chemical Engineering, Aragon Institute of Nanoscience (INA), University of Zaragoza, Campus Río Ebro-Edificio I+D, C/ Poeta Mariano Esquillor S/N, 50018-Zaragoza, Spain.

Developing hybrid poly(N-isopropylacrylamide)-based nanogels decorated with plasmonic hollow gold nanoparticles for on-demand drug delivery and their physico-chemical characterization, bupivacaine loading and release ability upon light irradiation, and cell viability. Hollow gold nanoparticles were prepared by galvanic replacement reaction; poly(N-isopropylacrylamide)-based nanogels were synthesized via precipitation polymerization and their electrostatic coupling was accomplished using poly(allylamine hydrochloride) as cationic polyelectrolyte linker. Colloidal stability of the resulted hybrid nanovectors was demonstrated under physiological conditions together with their fast response and excellent heating efficiency after light stimulation, indicating their potential use as triggered drug-delivery vectors. Moreover, their influence on cell metabolism and cell cycle under subcytotoxic doses were studied showing excellent cytocompatibility.
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http://dx.doi.org/10.2217/nnm-2019-0270DOI Listing
February 2020

Gas-Directed Production of Noble Metal-Magnetic Heteronanostructures in Continuous Fashion: Application in Catalysis.

ACS Appl Mater Interfaces 2019 Nov 11;11(46):43520-43532. Epub 2019 Nov 11.

Institute of Nanoscience of Aragon and Department of Chemical Engineering , University of Zaragoza , E-50018 Zaragoza , Spain.

Complex nanomaterials produced by scale-up batch processes lack suitable control of shape, size distribution, chemical composition, and quality, because heat and mass transfer are seriously affected as the reactor volume increases. Here we use a novel continuous synthesis procedure, the active gas-liquid segmented flow, to produce noble metal-magnetic heteronanostructures with enormous interest in the fields of catalysis, biomedicine, environmental sensors, food monitoring, and chemical analysis. The microreactor technology proposed scales down the reaction volume to gain advantage of the large surface area to volume ratio with respect to conventional batch-type reactors, improving heat and mass transport and, consequently, promoting a uniform heating and mixing. The gas phase was introduced in the chemical reactor as gas slugs of nanoliter scale with a dual role: (1) passive mixing and (2) chemical directing agent to tune the crystallization of nanostructures in a continuous fashion. The shape, size, and magnetic properties of the resulting heteronanostructures, as well as the density, size, and composition of noble metal nanoparticles were tuned to show the versatility of the proposed approach in a timeline of 4 min. We demonstrated that the produced nanostructures provide excellent catalytic properties in the catalyzed hydrogenation of nitrophenols to aminophenols. Electron microscopy, UV-vis spectroscopy, and cyclic voltammetry studies showed the remarkable catalytic performance of the produced heteronanostructures.
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http://dx.doi.org/10.1021/acsami.9b15982DOI Listing
November 2019

Co-encapsulation of superparamagnetic nanoparticles and doxorubicin in PLGA nanocarriers: Development, characterization and in vitro antitumor efficacy in glioma cells.

Eur J Pharm Biopharm 2019 Dec 16;145:65-75. Epub 2019 Oct 16.

Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra, C/Irunlarrea 1, E-31008 Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain. Electronic address:

With a very poor prognosis and no clear etiology, glioma is the most aggressive cancer in the brain. Thanks to its versatility, nanomedicine is a promising option to overcome the limitations on chemotherapy imposed by the blood brain barrier (BBB). The objective of this paper was to obtain monitored tumor-targeted therapeutic nanoparticles (NPs). To that end, theranostic surfactant-coated polymer poly-Lactic-co-Glycolic Acid (PLGA) nanoplatform encapsulating doxorubicin hydrochloride (DOX) and superparamagnetic iron oxide NPs (SPIONs) were developed. Different non-ionic surfactants known as BBB crossing enhancers (Tween 80, Brij-35, Pluronic F68 or Vitamin E-TPGS) were used to develop 4 types of theranostic nanoplatforms, which were characterized in terms of size and morphology by DLS, TEM and STEM-HAADF analyses. Moreover, the 3-month stability test, the therapeutic efficacy against different glioma cell lines (U87-MG, 9L/LacZ and patient derived-neuronal stem cells) and the Magnetic Resonance Imaging (MRI) relaxivity were studied. Results showed that the synthesised nanoplatforms were stable at 4 °C after their lyophilization, being that of paramount importance to ensure a long-term stability in a future in vivo application. Furthermore, the theranostic nanoplatforms were efficient in the in vitro treatment of glioma cells, proving to have imaging efficacy as MRI contrast agents. Our results show an efficient loading of drugs and good value of the relaxivity. Therefore, the efficient theranostic hybrid nanoplatform developed here could be used to perform MRI-guided delivery of hydrophobic drugs.
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http://dx.doi.org/10.1016/j.ejpb.2019.10.004DOI Listing
December 2019

The Effect of Titanium Dioxide Surface Modification on the Dispersion, Morphology, and Mechanical Properties of Recycled PP/PET/TiO PBNANOs.

Polymers (Basel) 2019 Oct 16;11(10). Epub 2019 Oct 16.

POLYMAT and Polymer Science and Technology Department, Faculty of Chemistry, University of the Basque Country UPV/EHU, Paseo Manuel de Lardizabal 3, 20018 Donostia-San Sebastián, Spain.

Titanium dioxide (TiO) nanoparticles have recently appeared in PET waste because of the introduction of opaque PET bottles. We prepare polymer blend nanocomposites (PBNANOs) by adding hydrophilic (hphi), hydrophobic (hpho), and hydrophobically modified (hphoM) titanium dioxide (TiO) nanoparticles to 80rPP/20rPET recycled blends. Contact angle measurements show that the degree of hydrophilicity of TiO decreases in the order hphi > hpho > hphoM. A reduction of rPET droplet size occurs with the addition of TiO nanoparticles. The hydrophilic/hydrophobic balance controls the nanoparticles location. Transmission electron microscopy (TEM_ shows that hphi TiO preferentially locates inside the PET droplets and hpho at both the interface and PP matrix. HphoM also locates within the PP matrix and at the interface, but large loadings (12%) can completely cover the surfaces of the droplets forming a physical barrier that avoids coalescence, leading to the formation of smaller droplets. A good correlation is found between the crystallization rate of PET (determined by DSC) and nanoparticles location, where hphi TiO induces the highest PET crystallization rate. PET lamellar morphology (revealed by TEM) is also dependent on particle location. The mechanical behavior improves in the elastic regime with TiO addition, but the plastic deformation of the material is limited and strongly depends on the type of TiO employed.
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http://dx.doi.org/10.3390/polym11101692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835408PMC
October 2019

Cancer-derived exosomes loaded with ultrathin palladium nanosheets for targeted bioorthogonal catalysis.

Nat Catal 2019 Oct 9;2(10):864-872. Epub 2019 Sep 9.

Cancer Research UK Edinburgh Centre, MRC Institute of Genetics & Molecular Medicine, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XR, UK.

The transformational impact of bioorthogonal chemistries has inspired new strategies for the synthesis of bioactive agents through non-natural means. Among these, palladium (Pd) catalysts have played a prominent role in the growing subfield of bioorthogonal catalysis by producing xenobiotics and uncaging biomolecules in living systems. However, delivering catalysts selectively to specific cell types still lags behind catalyst development. Here we have developed a bio-artificial device consisting of cancer-derived exosomes loaded with Pd catalysts by a method that enables the controlled assembly of Pd nanosheets directly inside the vesicles. This hybrid system mediates Pd-triggered dealkylation reactions and inside cells and displays preferential tropism for their progenitor cells. The use of Trojan exosomes to deliver abiotic catalysts into designated cancer cells creates the opportunity for a new targeted therapy modality: exosome-directed catalyst prodrug therapy, whose first steps are presented herein with the cell-specific release of the anticancer drug panobinostat.
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http://dx.doi.org/10.1038/s41929-019-0333-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6795537PMC
October 2019

Targeted Release of Probiotics from Enteric Microparticulated Formulations.

Polymers (Basel) 2019 Oct 13;11(10). Epub 2019 Oct 13.

Department of Chemical Engineering. Aragón Institute of Nanoscience (INA), University of Zaragoza, Campus Río Ebro-Edificio I+D, C/ Poeta Mariano Esquillor S/N, 50018-Zaragoza, Spain.

The development of advanced probiotic delivery systems, which preserve bacteria from degradation of the gastrointestinal tract and achieve a targeted release mediated by pH-independent swelling, is of great interest to improve the efficient delivery of probiotic bacteria to the target tissue. Gram-positive and Gram-negative bacteria models ( (Moro) Hansen and Mocquot (ATCC® 4356™) and S17, respectively) have been successfully encapsulated for the first time in pH-independent microparticulate polymethacrylates (i.e., Eudraguard biotic) used for the targeted delivery of nutraceuticals to the colon. These bacteria have also been encapsulated within the mucoadhesive polymethacrylate Eudragit RS 100 widely used as targeted release formulation for active pharmaceutical ingredients. The enteric microparticles remained unaltered under simulated gastric conditions and released the contained viable microbial cargo under simulated intestinal conditions. Buoyancies of 90.2% and 57.3% for Eudragit and Eudraguard microparticles, respectively, and long-term stability (5 months) for the encapsulated microorganisms were found. Cytotoxicity of the microparticles formulated with both polymers was evaluated (0.5-20 mg/mL) on Caco-2 cells, showing high cytocompatibility. These results underline the suitability of the synthesized materials for the successful delivery of probiotic formulations to the target organ, highlighting for the first time the potential use of Eudraguard biotic as an effective enteric coating for the targeted delivery of probiotics.
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http://dx.doi.org/10.3390/polym11101668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835770PMC
October 2019

Efficient encapsulation of theranostic nanoparticles in cell-derived exosomes: leveraging the exosomal biogenesis pathway to obtain hollow gold nanoparticle-hybrids.

Nanoscale 2019 Oct 9;11(40):18825-18836. Epub 2019 Oct 9.

Networking Research Center of Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN, 28029-Madrid, Spain and Instituto Aragonés de Ciencias de la Salud (IACS), Centro de Investigación Biomédica de Aragón (CIBA), 50009-Zaragoza, Spain and IIS Aragón(IISA), Centro de Investigación Biomédica de Aragón (CIBA), 50009-Zaragoza, Spain and Fundación ARAID. Avda. Ranillas, 1-D, planta 2ª, oficina b, 50018-Zaragoza, Spain.

Exosomes can be considered natural targeted delivery systems able to carry exogenous payloads, drugs or theranostic nanoparticles (NPs). This work aims to combine the therapeutic capabilities of hollow gold nanoparticles (HGNs) with the unique tumor targeting properties provided by exosomes. Here, we tested different methods to encapsulate HGNs (capable of absorbing light in the NIR region for selective thermal ablation) into murine melanoma cells derived exosomes (B16-F10-exos), including electroporation, passive loading by diffusion, thermal shock, sonication and saponin-assisted loading. These methods gave less than satisfactory results: although internalization of relatively large NPs into B16-F10-exos was achieved by almost all the physicochemical methods tested, only about 15% of the exosomes were loaded with NPs and several of those processes had a negative effect regarding the morphology and integrity of the loaded exosomes. In a different approach, B16-F10 cells were pre-incubated with PEGylated HGNs (PEG-HGNs) in an attempt to incorporate the NPs into the exosomal biogenesis pathway. The results were highly successful: exosomes recovered from the supernatant of the cell culture showed up to 50% of HGNs internalization. The obtained hybrid HGN-exosome vectors were characterized with a battery of techniques to make sure that internalization of HGNs did not affect exosome characteristics compared with other strategies. PEG-HGNs were released through the endosomal-exosome biogenesis pathway confirming that the isolated vesicles were exosomes.
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http://dx.doi.org/10.1039/c9nr06183eDOI Listing
October 2019

Gold nanoparticles for the in situ polymerization of near-infrared responsive hydrogels based on fibrin.

Acta Biomater 2019 12 27;100:306-315. Epub 2019 Sep 27.

Hospital Universitario La Paz-IdiPAZ, Paseo de la Castellana 261, Madrid 28046 Spain; CIBER de Bioingenieria, Biomateriales y Nanomedicina, CIBER-BBN, Spain. Electronic address:

Non-invasiveness and relative safety of photothermal therapy, which enables local hyperthermia of target tissues using a near infrared (NIR) laser, has attracted increasing interest. Due to their biocompatibility, amenability of synthesis and functionalization, gold nanoparticles have been investigated as therapeutic photothermal agents. In this work, hollow gold nanoparticles (HGNP) were coated with poly-l-lysine through the use of COOH-Poly(ethylene glycol)-SH as a covalent linker. The functionalized HGNP, which peak their surface plasmon resonance at 800 nm, can bind thrombin. Thrombin-conjugated HGNP conduct in situ fibrin polymerization, facilitating the process of generating photothermal matrices. Interestingly, the metallic core of thrombin-loaded HGNP fragmentates at physiological temperature. During polymerization process, matrices prepared with thrombin-loaded HGNP were loaded with genetically-modified stem cells that harbour a heat-activated and ligand-dependent gene switch for regulating transgene expression. NIR laser irradiation of resulting cell constructs in the presence of ligand successfully triggered transgene expression in vitro and in vivo. STATEMENT OF SIGNIFICANCE: Current technological development allows synthesis of gold nanoparticles (GNP) in a wide range of shapes and sizes, consistently and at scale. GNP, stable and easily functionalized, show low cytotoxicity and high biocompatibility. Allied to that, GNP present optoelectronic properties that have been exploited in a range of biomedical applications. Following a layer-by-layer functionalization approach, we prepared hollow GNP coated with a positively charged copolymer that enabled thrombin conjugation. The resulting nanomaterial efficiently catalyzed the formation of fibrin hydrogels which convert energy of the near infrared (NIR) into heat. The resulting NIR-responsive hydrogels can function as scaffolding for cells capable of controlled gene expression triggered by optical hyperthermia, thus allowing the deployment of therapeutic gene products in desired spatiotemporal frameworks.
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http://dx.doi.org/10.1016/j.actbio.2019.09.040DOI Listing
December 2019

Continuous Microfluidic Synthesis of Pd Nanocubes and PdPt Core-Shell Nanoparticles and Their Catalysis of NO Reduction.

ACS Appl Mater Interfaces 2019 Oct 28;11(39):36196-36204. Epub 2019 Aug 28.

Applied Chemistry, Department of Chemistry and Chemical Engineering , Chalmers University of Technology , 41296 Gothenburg , Sweden.

Faceted colloidal nanoparticles are currently of immense interest due to their unique electronic, optical, and catalytic properties. However, continuous flow synthesis that enables rapid formation of faceted nanoparticles of single or multi-elemental composition is not trivial. We present a continuous flow synthesis route for the synthesis of uniformly sized Pd nanocubes and PdPt core-shell nanoparticles in a single-phase microfluidic reactor, which enables rapid formation of shaped nanoparticles with a reaction time of 3 min. The PdPt core-shell nanoparticles feature a dendritic, high surface area with the Pt shell covering the Pd core, as verified using high-resolution scanning transmission electron microscopy and energy dispersive X-ray spectroscopy. The Pd nanocubes and PdPt core-shell particles are catalytically tested during NO reduction in the presence of H in a flow pocket reactor. The Pd nanocubes exhibited low-temperature activity (i.e., <136 °C) and poor selectivity performance toward production of NO or N, whereas PdPt core-shell nanoparticles showed higher activity and were found to achieve better selectivity during NO reduction retaining its basic structure at relatively elevated temperatures, making the PdPt core-shell particles a unique, desirable synergic catalyst material for potential use in NO abatement processes.
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http://dx.doi.org/10.1021/acsami.9b09701DOI Listing
October 2019

The role of clonal communication and heterogeneity in breast cancer.

BMC Cancer 2019 Jul 5;19(1):666. Epub 2019 Jul 5.

Translational Molecular Pathology Group, Vall d'Hebron Research Institute, Barcelona, Spain.

Background: Cancer is a rapidly evolving, multifactorial disease that accumulates numerous genetic and epigenetic alterations. This results in molecular and phenotypic heterogeneity within the tumor, the complexity of which is further amplified through specific interactions between cancer cells. We aimed to dissect the molecular mechanisms underlying the cooperation between different clones.

Methods: We produced clonal cell lines derived from the MDA-MB-231 breast cancer cell line, using the UbC-StarTrack system, which allowed tracking of multiple clones by color: GFP C3, mKO E10 and Sapphire D7. Characterization of these clones was performed by growth rate, cell metabolic activity, wound healing, invasion assays and genetic and epigenetic arrays. Tumorigenicity was tested by orthotopic and intravenous injections. Clonal cooperation was evaluated by medium complementation, co-culture and co-injection assays.

Results: Characterization of these clones in vitro revealed clear genetic and epigenetic differences that affected growth rate, cell metabolic activity, morphology and cytokine expression among cell lines. In vivo, all clonal cell lines were able to form tumors; however, injection of an equal mix of the different clones led to tumors with very few mKO E10 cells. Additionally, the mKO E10 clonal cell line showed a significant inability to form lung metastases. These results confirm that even in stable cell lines heterogeneity is present. In vitro, the complementation of growth medium with medium or exosomes from parental or clonal cell lines increased the growth rate of the other clones. Complementation assays, co-growth and co-injection of mKO E10 and GFP C3 clonal cell lines increased the efficiency of invasion and migration.

Conclusions: These findings support a model where interplay between clones confers aggressiveness, and which may allow identification of the factors involved in cellular communication that could play a role in clonal cooperation and thus represent new targets for preventing tumor progression.
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http://dx.doi.org/10.1186/s12885-019-5883-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612119PMC
July 2019

Differences in levan nanoparticles depending on their synthesis route: Microbial vs cell-free systems.

Int J Biol Macromol 2019 Sep 27;137:62-68. Epub 2019 Jun 27.

Department of Chemical Engineering, University of Salamanca, Plaza Los Caídos s/n, Salamanca, Spain; Institute for Biomedical Research of Salamanca (IBSAL), Paseo de San Vicente, 58-182, Salamanca, Spain. Electronic address:

Differences between the levan obtained from bacteria and from cell-free systems were studied in this work. Results showed that both polymers are non-porous solids (type II isotherm with 20 m/g) with a main thermal decomposition at 200 °C and a negligible value of protein adsorption. Microbial levan produced nanoparticles of 90 nm in diameter whereas nanoparticles of 110 nm were obtained with the polymer obtained from a cell-free system. Both polymers behave as aggregates depending on the critical aggregation concentration. At the same time, that concentration depends on the technique used for the polymer synthesis. Cell-free system aggregation concentration is 0.24 mg/mL whereas a concentration of 0.05 mg/mL was found for the microbial system. In both cases, the average molecular weight of the aggregate is higher than 2000 kDa. These results highlight the existence of aggregation equilibrium for both polymers that has to be taken into account for future applications.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.06.128DOI Listing
September 2019

National health information systems for achieving the Sustainable Development Goals.

BMJ Open 2019 05 16;9(5):e027689. Epub 2019 May 16.

Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Objectives: Achieving the Sustainable Development Goals will require data-driven public health action. There are limited publications on national health information systems that continuously generate health data. Given the need to develop these systems, we summarised their current status in low-income and middle-income countries.

Setting: The survey team jointly developed a questionnaire covering policy, planning, legislation and organisation of case reporting, patient monitoring and civil registration and vital statistics (CRVS) systems. From January until May 2017, we administered the questionnaire to key informants in 51 Centers for Disease Control country offices. Countries were aggregated for descriptive analyses in Microsoft Excel.

Results: Key informants in 15 countries responded to the questionnaire. Several key informants did not answer all questions, leading to different denominators across questions. The Ministry of Health coordinated case reporting, patient monitoring and CRVS systems in 93% (14/15), 93% (13/14) and 53% (8/15) of responding countries, respectively. Domestic financing supported case reporting, patient monitoring and CRVS systems in 86% (12/14), 75% (9/12) and 92% (11/12) of responding countries, respectively. The most common uses for system-generated data were to guide programme response in 100% (15/15) of countries for case reporting, to calculate service coverage in 92% (12/13) of countries for patient monitoring and to estimate the national burden of disease in 83% (10/12) of countries for CRVS. Systems with an electronic component were being used for case reporting, patient monitoring, birth registration and death registration in 87% (13/15), 92% (11/12), 77% (10/13) and 64% (7/11) of responding countries, respectively.

Conclusions: Most responding countries have a solid foundation for policy, planning, legislation and organisation of health information systems. Further evaluation is needed to assess the quality of data generated from systems. Periodic evaluations may be useful in monitoring progress in strengthening and harmonising these systems over time.
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http://dx.doi.org/10.1136/bmjopen-2018-027689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530305PMC
May 2019

Size-Tailored Design of Highly Monodisperse Lipid Nanocapsules for Drug Delivery.

J Biomed Nanotechnol 2019 Jun;15(6):1149-1161

The empirical development of nanocarriers has unfortunately led to high attrition rates in clinical trials. This underpins the importance of the rational design of nanomedicines to achieve efficient disease-driven therapies. Since particle size certainly influences behaviour, rational disease-driven colloid design can only be achieved by determining the parameters that accurately control their size distribution. To this end, we have thoroughly revisited the parameters that drive the phase-inversion temperature nanoemulsification method to obtain kinetically stable and monodisperse lipid nanocapsules. Notably, we have evidenced that the major parameter driving nanocapsule formation is the oily phase/surfactant ratio and consequently, we have established a linear univariate mathematical model that predicts the particle size distribution for various oily phase-surfactant combinations (² > 0 99). Furthermore, we have observed that the difference between the HLB values of the surfactants and the triglycerides utilized as oily phase correlates with the steepness of the slope of the linear mathematical model. This model will bring the implementation of size-tailored lipid drug carriers determined by pathophysiological features a step closer. Importantly, this model pioneeringly fits all data available in the literature on size distribution of colloids prepared by low-energy methods and that were originally evaluated following other parameters. Moreover, the nanocapsules have been obtained following a single-step process, with the ensuing potential for a future scale-up in an energetically-efficient manner. These findings will eventually enable nanomedicines to be obtained "on-demand" to meet disease-driven criteria in terms of particle size and will also increase their chances of success.
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http://dx.doi.org/10.1166/jbn.2019.2765DOI Listing
June 2019