Lactic acid bacteria : reviewing the potential of a promising delivery live vector for biomedical purposes

Lactic acid bacteria (LAB) have a long history of safe exploitation by humans, being used for centuries in food production and preservation and as probiotic agents to promote human health. Interestingly, some species of these Gram-positive bacteria, which are generally recognized as safe organisms by the US Food and Drug Administration (FDA), are able to survive through the gastrointestinal tract (GIT), being capable to reach and colonize the intestine, where they play an important role. Besides, during the last decades, an important effort has been done for the development of tools to use LAB as microbial cell factories for the production of proteins of interest. Given the need to develop effective strategies for the delivery of prophylactic and therapeutic molecules, LAB have appeared as an appealing option for the oral, intranasal and vaginal delivery of such molecules. So far, these genetically modified organisms have been successfully used as vehicles for delivering functional proteins to mucosal tissues in the treatment of many different pathologies including GIT related pathologies, diabetes, cancer and viral infections, among others. Interestingly, the administration of such microorganisms would suppose a significant decrease in the production cost of the treatments agents since being live organisms, such vectors would be able to autonomously amplify and produce and deliver the protein of interest. In this context, this review aims to provide an overview of the use of LAB engineered as a promising alternative as well as a safety delivery platform of recombinant proteins for the treatment of a wide range of diseases

Editorial: High added-value nanoparticles: Rethinking and recycling cell protein waste

info:eu-repo/semantics/publishedVersio

Editorial: High added-value nanoparticles: Rethinking and recycling cell protein waste

Extracellular vesicles; Biomedicine; NanobiotechnlogyVesículas extracelulares; Biomedicina; NanobiotecnologíaVesícules extracel·lulars; Biomedicina; Nanobiotecnologi

I am uncertain” vs “it is uncertain”. How linguistic markers of the uncertainty source affect uncertainty communication

Two psychological sources of uncertainty bear implications for judgment and decision-making: external uncertainty is seen as stemming from properties of the world, whereas internal uncertainty is seen as stemming from lack of knowledge. The apparent source of uncertainty can be conveyed through linguistic markers, such as the pronoun of probability phrases (e.g., I am uncertain vs. It is uncertain). Here, we investigated whether and when speakers use different pronoun subjects as such linguistic markers (Exp. 1 and 2) and what hearers infer from them (Exp. 3 and 4). Speakers more often described higher probabilities and knowable outcomes with internal probability phrases. In dialogue, speakers mirrored the source of their conversational partner. Markers of the source had a main effect or interacted with the probability conveyed and speaker expertise to shape the judgments and decisions of hearers. For example, experts voicing an internal probability phrase were judged as more knowledgeable than experts using an external probability phrase whereas the result was the opposite for lay speakers. We discuss how these findings inform our understanding of subjective uncertainty and uncertainty communication theories

Isolation of cell-free bacterial inclusion bodies

Background: Bacterial inclusion bodies are submicron protein clusters usually found in recombinant bacteria that have been traditionally considered as undesirable products from protein production processes. However, being fully biocompatible, they have been recently characterized as nanoparticulate inert materials useful as scaffolds for tissue engineering, with potentially wider applicability in biomedicine and material sciences. Current protocols for inclusion body isolation from Escherichia coli usually offer between 95 to 99% of protein recovery, what in practical terms, might imply extensive bacterial cell contamination, not compatible with the use of inclusion bodies in biological interfaces. Results: Using an appropriate combination of chemical and mechanical cell disruption methods we have established a convenient procedure for the recovery of bacterial inclusion bodies with undetectable levels of viable cell contamination, below 10-1 cfu/ml, keeping the particulate organization of these aggregates regarding size and protein folding features. Conclusions: The application of the developed protocol allows obtaining bacterial free inclusion bodies suitable for use in mammalian cell cultures and other biological interfaces

Perspectives of nano-carrier drug delivery systems to overcome cancer drug resistance in the clinics

Sistemes d'administració de fàrmacs; Resistència; Tractament del càncerSistemas de administración de fármacos; Resistencia; Tratamiento del cancerDrug delivery systems; Resistance; Cancer treatmentAdvanced cancer is still considered an incurable disease because of its metastatic spread to distal organs and progressive gain of chemoresistance. Even though considerable treatment progress and more effective therapies have been achieved over the past years, recurrence in the long-term and undesired side effects are still the main drawbacks of current clinical protocols. Moreover, a majority of chemotherapeutic drugs are highly hydrophobic and need to be diluted in organic solvents, which cause high toxicity, in order to reach effective therapeutic dose. These limitations of conventional cancer therapies prompted the use of nanomedicine, the medical application of nanotechnology, to provide more effective and safer cancer treatment. Potential of nanomedicines to overcome resistance, ameliorate solubility, improve pharmacological profile, and reduce adverse effects of chemotherapeutical drugs is thus highly regarded. Their use in the clinical setting has increased over the last decade. Among the various existing nanosystems, nanoparticles have the ability to transform conventional medicine by reducing the adverse effects and providing a controlled release of therapeutic agents. Also, their small size facilitates the intracellular uptake. Here, we provide a closer review of clinical prospects and mechanisms of action of nanomedicines to overcome drug resistance. The significance of specific targeting towards cancer cells is debated as well

Cancer stem cell-derived extracellular vesicles preferentially target MHC-II–macrophages and PD1+ T cells in the tumor microenvironment

Cèl·lules mare del càncer; Càncers de cap i coll; MacròfagsCancer stem cells; Head and neck cancers; MacrophagesCélulas madre del cáncer; Cánceres de cabeza y cuello; MacrófagosImmunotherapy is an approved treatment option for head and neck squamous cell carcinoma (HNSCC). However, the response rate to immune checkpoint blockade is only 13% for recurrent HNSCC, highlighting the urgent need to better understand tumor-immune interplay, with the ultimate goal of improving patient outcomes. HNSCC present high local recurrence rates and therapy resistance that can be attributed to the presence of cancer stem cells (CSC) within tumors. CSC exhibit singular properties that enable them to avoid immune detection and eradication. How CSC communicate with immune cells and which immune cell types are preferentially found within the CSC niche are still open questions. Here, we used genetic approaches to specifically label CSC-derived extracellular vesicles (EVs) and to perform Sortase-mediated in vivo proximity labeling of CSC niche cells. We identified specific immune cell subsets that were selectively targeted by EVCSC and that were found in the CSC niche. Native EVCSC preferentially targeted MHC-II–macrophages and PD1+ T cells in the tumor microenvironment, which were the same immune cell subsets enriched within the CSC niche. These observations indicate that the use of genetic technologies able to track EVs without in vitro isolation are a valuable tool to unveil the biology of native EVCSC.European Molecular Biology Organization (EMBO):Patricia Gonzalez-Callejo short-term fellowship; V Foundation for Cancer Research (VFCR):Natalie M Claudio,Ferdinando Pucci 2019-012

Producció d'amiloides bacterians lliures de toxines

Els cossos d'inclusió o amiloides són agregats de proteïnes nanoestructurades produïdes a l'interior d'una cèl·lula, freqüents en determinats bacteris, i amb interessants aplicacions biomèdiques, com ara l'alliberament de fàrmacs proteics. Fins ara, l'ús dels cossos d'inclusió estava limitat per la presència de toxines pròpies de les cèl·lules bacterianes que els produïen. Un estudi ha desenvolupat diverses soques d'Escherichia coli sense aquestes toxines a partir de les quals s'ha pogut produir amiloides lliures de contaminants potencialment perillosos.Los cuerpos de inclusión o amiloides son agregados de proteínas nanoestructuradas producidas en el interior de una célula, frecuentes en determinadas bacterias, y con interesantes aplicaciones biomédicas, tales como la liberación de fármacos proteicos. Hasta ahora, el uso de los cuerpos de inclusión estaba limitado por la presencia de toxinas propias de las células bacterianas que los producían. Un estudio ha desarrollado diversas cepas de Escherichia coli sin estas toxinas a partir de las cuales se ha podido producir amiloides libres de contaminantes potencialmente peligrosos.Inclusion bodies or amyloids are nanostructured protein aggregates produced inside a cell, frequent in certain bacteria, and with interesting biomedical applications such as drug protein delivery. Until now, the use of inclusion bodies was limited by the presence of own toxins from the producing bacterial cells. A study has developed several toxin-free Escherichia coli strains from which amyloids free from potentially hazardous cell contaminants have been produced

Selectively Targeting Breast Cancer Stem Cells by 8-Quinolinol and Niclosamide

Cancer stem cells; Combination therapy; NiclosamideCélulas madre cancerosas; Terapia combinada; NiclosamidaCèl·lules mare cancerígenes; Teràpia combinada; NiclosamidaCancer maintenance, metastatic dissemination and drug resistance are sustained by cancer stem cells (CSCs). Triple negative breast cancer (TNBC) is the breast cancer subtype with the highest number of CSCs and the poorest prognosis. Here, we aimed to identify potential drugs targeting CSCs to be further employed in combination with standard chemotherapy in TNBC treatment. The anti-CSC efficacy of up to 17 small drugs was tested in TNBC cell lines using cell viability assays on differentiated cancer cells and CSCs. Then, the effect of 2 selected drugs (8-quinolinol -8Q- and niclosamide -NCS-) in the cancer stemness features were evaluated using mammosphere growth, cell invasion, migration and anchorage-independent growth assays. Changes in the expression of stemness genes after 8Q or NCS treatment were also evaluated. Moreover, the potential synergism of 8Q and NCS with PTX on CSC proliferation and stemness-related signaling pathways was evaluated using TNBC cell lines, CSC-reporter sublines, and CSC-enriched mammospheres. Finally, the efficacy of NCS in combination with PTX was analyzed in vivo using an orthotopic mouse model of MDA-MB-231 cells. Among all tested drug candidates, 8Q and NCS showed remarkable specific anti-CSC activity in terms of CSC viability, migration, invasion and anchorage independent growth reduction in vitro. Moreover, specific 8Q/PTX and NCS/PTX ratios at which both drugs displayed a synergistic effect in different TNBC cell lines were identified. The sole use of PTX increased the relative presence of CSCs in TNBC cells, whereas the combination of 8Q and NCS counteracted this pro-CSC activity of PTX while significantly reducing cell viability. In vivo, the combination of NCS with PTX reduced tumor growth and limited the dissemination of the disease by reducing circulating tumor cells and the incidence of lung metastasis. The combination of 8Q and NCS with PTX at established ratios inhibits both the proliferation of differentiated cancer cells and the viability of CSCs, paving the way for more efficacious TNBC treatments.This work was supported by the Instituto de Salud Carlos III (ISCiii), through Networking Research Center on Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN), an initiative that also counts with the assistance from the European Regional Development Fund (ERDF), specifically in the PENTRI-2 Project and by the “Fundació Marató TV3” (337/C/2013) to I.A., M.R. and E.V. Our laboratories were also supported by the Fondo de Investigaciones Sanitarias (FIS, grants PI20/1474 to S.S.J. and PI18/00871 and PI21/00936), co-financed by the ERDF and the 2017-SGR-638 of the Catalan Government to S.S.J. and EvoNano Project (GA800983), funded by European Union’s Horizon 2020 FET Open Programme. N.G.-A. was supported by grants from Pla Estratègic de Recerca i Innovació en Salut (PERIS) of Catalonia (SLT006/17/00270 270)