Despite promising in vitro evidence for effective glioblastoma treatment, most drugs are hindered from entering the central nervous system because of the presence of the blood-brain barrier (BBB). Thus, successful modification of drug delivery and novel therapeutic strategies are needed to overcome this obstacle. Extracellular vesicles (EVs), cell-derived membrane-encapsulated structures with diameters ranging from 50 to 1000 nm, have been explored as the drug delivery system to deliver their cargo to the brain tissue. Moreover, tumor targeting and selective drug delivery has been facilitated by engineering their parent cells to secrete modified EVs. However, the method suffers from many shortcomings including poor repeatability and complex and time-consuming operations. In this context, we present an easy-to-adapt and highly versatile methodology to modify EVs with an engineered peptide capable of recognition and eradication of glioma. On the basis of molecular recognition between phospholipids on EV lipid bilayer membranes and ApoA-I mimetic peptides, we have developed methotrexate (MTX)-loaded EVs functionalized with therapeutic [Lys-Leu-Ala (KLA)] and targeted [low-density lipoprotein (LDL)] peptides. In vitro experiments demonstrated that EVs decorated with LDL or KLA-LDL could obviously ameliorate their uptake by human primary glioma cell line U87 and permeation into three-dimensional glioma spheroids in contrast to blank EVs, and consequently, the treatment outcome of the payload is improved. Both ex vivo and in vivo imaging experiments revealed that peptide LDL could obviously promote EV extravasation across the BBB and distribution in the glioma site. Furthermore, compared with the mice administrated with MTX and MTX@EVs, MTX@EVs-KLA-LDL-treated mice showed the longest median survival period. In conclusion, functionalizing with the peptide onto EV surfaces may provide a substantial advancement in the application of EVs for selective target binding as well as therapeutic effects for brain tumor treatment.

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Integrating biomedical imaging and multimodal therapies into one platform for enhanced anticancer efficacy is of great significance. Herein, a core/shell structured nanotheranostic (CuS@copolymer) for magnetic resonance imaging (MRI)-guided chemo-photothermal therapy was simply prepared via emulsifier-free emulsion polymerization with the full participation of hydrophilic CuS NPs, styrene (St), N-isopropylacrylamide (NIPAm), methacrylic acid (MAA), and polymerizable rare earth complex (Gd­(AA)3phen). The synthesized multifunctional microspheres with excellent biocompatibility exhibited high loading capacity (15.3 wt %) for DOX·HCl and excellent drug release under low pH and high temperature. The photosensitive CuS cores which can simultaneously efficiently absorb near-infrared (NIR) light and convert NIR light to fatal heat, leading to a synergistic therapeutic effect combined photothermal therapy (PTT) with chemotherapy. Moreover, the temperature sensitive copolymer attached onto the CuS nanoparticles was able to be productively infected by the thermal effect and give rise to a highly controllable DOX release. Furthermore, the CuS@copolymer/DOX showed an enhanced therapeutic efficacy against 4T1 cells than separate photothermal therapy or chemotherapy. Additionally, the drug delivery procedure could be visualized by in vivo MR images and the longitudinal relaxivity (r 1) was calculated to be 10.72 mM–1 s–1. These results suggest the CuS@copolymer microspheres highly attractive candidates for biomedical applications.

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BackgroundPotassium (K) deficiency in arable land is one of the most important factors affecting crop productivity. Development of low K (LK) tolerant crop cultivars is regarded as a best economic and effective approach for solving the issue of LK. In previous studies, we found a wider variation of LK tolerance in the Tibetan wild barley accessions than cultivated barley. However, the mechanism of LK tolerance in wild barley is still elusive.ResultsIn this study, two wild barley genotypes (XZ153, LK tolerant and XZ141, LK sensitive) and one cultivar (LuDaoMai, LK tolerant) was used to investigate metabolome changes in response to LK stress. Totally 57 kinds of metabolites were identified in roots and leaves of three genotypes at 16 d after LK treatment. In general, accumulation of amino acids and sugars was enhanced in both roots and leaves, while organic acids were reduced under LK stress compared to the control. Meanwhile, the concentrations of the negatively charged amino acids (Asp and Glu) and most organic acids was reduced in both roots and leaves, but more positively charged amino acids (Lys and Gln) were increased in three genotypes under LK. XZ153 had less reduction than other two genotypes in biomass and chlorophyll content under LK stress and showed greater antioxidant capacity as reflected by more synthesis of active oxygen scavengers. Higher LK tolerance of XZ153 may also be attributed to its less carbohydrate consumption and more storage of glucose and other sugars, thus providing more energy for plant growth under LK stress. Moreover, phenylpropanoid metabolic pathway mediated by PAL differed among three genotypes, which is closely associated with the genotypic difference in LK tolerance.ConclusionsLK tolerance in the wild barley is attributed to more active phenylpropanoid metabolic pathway mediated by PAL, energy use economy by reducing carbohydrate consumption and storage of glucose and other sugars, and higher antioxidant defense ability under LK stress.Electronic supplementary materialThe online version of this article (10.1186/s12870-018-1404-4) contains supplementary material, which is available to authorized users.

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Polypyrrole nanoparticle (PPy) based theranostic agents for magnetic resonance imaging (MRI) guided photothermal therapy (PTT) have received increasing attention in recent years.