BackgroundExosomes are considered key elements for communication between cells, but very little is known about the mechanisms and selectivity of the transference processes involving exosomes released from different cells.ResultsIn this study we have investigated the transfer of hollow gold nanoparticles (HGNs) between different cells when these HGNs were loaded within exosomes secreted by human placental mesenchymal stem cells (MSCs). These HGNs were successfully incorporated in the MSCs exosome biogenesis pathway and released as HGNs-loaded exosomes. Time-lapse microscopy and atomic emission spectroscopy allowed us to demonstrate the selective transfer of the secreted exosomes only to the cell type of origin when studying different cell types including cancer, metastatic, stem or immunological cells.ConclusionsIn this study we demonstrate the selectivity of in vitro exosomal transfer between certain cell types and how this phenomenon can be exploited to develop new specific vectors for advanced therapies. Specifically, we show how this preferential uptake can be leveraged to selectively induce cell death by light-induced hyperthermia only in cells of the same type as those producing the corresponding loaded exosomes. We describe how the exosomes are preferentially transferred to some cell types but not to others, thus providing a better understanding to design selective therapies for different diseases. Electronic supplementary materialThe online version of this article (10.1186/s12951-018-0437-z) contains supplementary material, which is available to authorized users.

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The ATP-binding cassette (ABC) transporter breast cancer resistance protein (BCRP)/ABCG2 is a high-capacity efflux transporter with wide substrate specificity located in apical membranes of epithelia, which is involved in drug availability. BCRP is responsible for the active secretion of clinically and toxicologically important substrates to milk. The present study shows BCRP expression in sheep and cow by immunoblotting with MAb (BXP-53). Vanadate-sensitive ATPase activity with specific BCRP substrates and inhibitors was measured in bovine mammary gland homogenates. To assess the role of BCRP in ruminant mammary gland we tested the fluoroquinolone enrofloxacin (ENRO). In polarized cell lines, ENRO was transported by Bcrp1/BCRP with secretory/absorptive ratios of 6.5 and 2 respectively. The efflux was blocked by the BCRP inhibitor Ko143. ENRO pharmacokinetics in plasma and milk was studied in sheep after co-administration of drug (2.5 mg/kg, i.v.) and genistein (0.8 mg/kg, i.m.) or albendazole sulfoxide (2 mg/kg, i.v) as BCRP inhibitors. Concomitant administration of BCRP inhibitors with ENRO had no significant effect on the plasma disposition kinetics of ENRO but decreased ENRO concentrations in milk.

A fast and effective wound healing process would substantially decrease medical costs, wound care supplies, and hospitalization significantly improving the patients’ quality of life. The search for effective therapeutic approaches seems to be imperative in order to avoid the aggravation of chronic wounds. In spite of all the efforts that have been made during the recent years towards the development of artificial wound dressings, none of the currently available options combine all the requirements necessary for quick and optimal cutaneous regeneration. Therefore, technological advances in the area of temporary and permanent smart dressings for wound care are required. The development of nanoscience and nanotechnology can improve the materials and designs used in topical wound care in order to efficiently release antimicrobial, anti-inflammatory and regenerative compounds speeding up the endogenous healing process. Nanostructured dressings can overcome the limitations of the current coverings and, separately, natural origin components can also overcome the drawbacks of current antibiotics and antiseptics (mainly cytotoxicity, antibiotic resistance, and allergies). The combination of natural origin components with demonstrated antibiotic, regenerative, or anti-inflammatory properties together with nanostructured materials is a promising approach to fulfil all the requirements needed for the next generation of bioactive wound dressings. Microbially compromised wounds have been treated with different essential oils, honey, cationic peptides, aloe vera, plant extracts, and other natural origin occurring antimicrobial, anti-inflammatory, and regenerative components but the available evidence is limited and insufficient to be able to draw reliable conclusions and to extrapolate those findings to the clinical practice. The evidence and some promising preliminary results indicate that future comparative studies are justified but instead of talking about the beneficial or inert effects of those natural origin occurring materials, the scientific community leads towards the identification of the main active components involved and their mechanism of action during the corresponding healing, antimicrobial, or regenerative processes and in carrying out systematic and comparative controlled tests. Once those natural origin components have been identified and their efficacy validated through solid clinical trials, their combination within nanostructured dressings can open up new avenues in the fabrication of bioactive dressings with outstanding characteristics for wound care. The motivation of this work is to analyze the state of the art in the use of different essential oils, honey, cationic peptides, aloe vera, plant extracts, and other natural origin occurring materials as antimicrobial, anti-inflammatory and regenerative components with the aim of clarifying their potential clinical use in bioactive dressings. We conclude that, for those natural occurring materials, more clinical trials are needed to reach a sufficient level ...

Even though essential oils (EOs) have been used for therapeutic purposes, there is now a renewed interest in the antimicrobial properties of phytochemicals and EOs in particular. Their demonstrated low levels of induction of antimicrobial resistance make them interesting for bactericidal applications, though their complex composition makes it necessary to focus on the study of their main components to identify the most effective ones. Herein, the evaluation of the antimicrobial action of different molecules present in EOs against planktonic and biofilm-forming Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria was assessed. The bactericidal mechanisms of the different molecules, as well as their cytocompatibility, were also studied. Carvacrol, cinnamaldehyde, and thymol exhibit the highest in vitro antimicrobial activities against E. coli and S. aureus, with membrane disruption the bactericidal mechanism identified. The addition of those compounds (≥0.5 mg/mL) hampers S. aureus biofilm formation and partially eliminates preformed biofilms. The subcytotoxic values of the tested EO molecules (0.015–0.090 mg/mL) are lower than the minimum inhibitory and bactericidal concentrations obtained for bacteria (0.2–0.5 mg/mL) but are higher than that obtained for chlorhexidine (0.004 mg/mL), indicating the reduced cytotoxicity of EOs. Therefore, carvacrol, cinnamaldehyde, and thymol are molecules contained in EOs that could be used against E. coli– and S. aureus–mediated infections without a potential induction of bactericidal resistance and with lower cell toxicity than the conventional widely used chlorhexidine.

BackgroundMesenchymal stem cells (MSCs) have been promoted as an attractive option to use as cellular delivery vehicles to carry anti-tumor agents, owing to their ability to home into tumor sites and secrete cytokines. Multiple isolated populations have been described as MSCs, but despite extensive in vitro characterization, little is known about their in vivo behavior.The aim of this study was to investigate the efficacy and efficiency of different MSC lineages derived from five different sources (bone marrow, adipose tissue, epithelial endometrium, stroma endometrium, and amniotic membrane), in order to assess their adequacy for cell-based anti-tumor therapies. Our study shows the crucial importance of understanding the interaction between MSCs and tumor cells, and provides both information and a methodological approach, which could be used to develop safer and more accurate targeted therapeutic applications.MethodsWe first measured the in vivo migration capacity and effect on tumor growth of the different MSCs using two imaging techniques: (i) single-photon emission computed tomography combined with computed tomography (SPECT-CT), using the human sodium iodine symporter gene (hNIS) and (ii) magnetic resonance imaging using superparamagnetic iron oxide. We then sought correlations between these parameters and expression of pluripotency-related or migration-related genes.ResultsOur results show that migration of human bone marrow-derived MSCs was significantly reduced and slower than that obtained with the other MSCs assayed and also with human induced pluripotent stem cells (hiPSCs). The qPCR data clearly show that MSCs and hiPSCs exert a very different pluripotency pattern, which correlates with the differences observed in their engraftment capacity and with their effects on tumor growth.ConclusionThis study reveals differences in MSC recruitment/migration toward the tumor site and the corresponding effects on tumor growth. Three observations stand out: 1) tracking of the stem cell is essential to check the safety and efficacy of cell therapies; 2) the MSC lineage to be used in the cell therapy needs to be carefully chosen to balance efficacy and safety for a particular tumor type; and 3) different pluripotency and mobility patterns can be linked to the engraftment capacity of the MSCs, and should be checked as part of the clinical characterization of the lineage.

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