@article{MTMT:34856989, title = {Synergistic induction of blood–brain barrier properties}, url = {https://m2.mtmt.hu/api/publication/34856989}, author = {Porkoláb, Gergő and Mészáros, Mária and Szecskó, Anikó and Vigh, Judit Piroska and Walter, Fruzsina and Figueiredo, Ricardo and Kálomista, Ildikó and Hoyk, Zsófia and Vizsnyiczai, Gaszton and Gróf, Ilona and Jan, Jeng-Shiung and Gosselet, Fabien and Pirity, Melinda and Vastag, Monika and Hudson, Natalie and Campbell, Matthew and Veszelka, Szilvia and Deli, Mária Anna}, doi = {10.1073/pnas.2316006121}, journal-iso = {P NATL ACAD SCI USA}, journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, volume = {121}, unique-id = {34856989}, issn = {0027-8424}, abstract = {Blood–brain barrier (BBB) models derived from human stem cells are powerful tools to improve our understanding of cerebrovascular diseases and to facilitate drug development for the human brain. Yet providing stem cell–derived endothelial cells with the right signaling cues to acquire BBB characteristics while also retaining their vascular identity remains challenging. Here, we show that the simultaneous activation of cyclic AMP and Wnt/β-catenin signaling and inhibition of the TGF-β pathway in endothelial cells robustly induce BBB properties in vitro. To target this interaction, we present a small-molecule cocktail named cARLA, which synergistically enhances barrier tightness in a range of BBB models across species. Mechanistically, we reveal that the three pathways converge on Wnt/β-catenin signaling to mediate the effect of cARLA via the tight junction protein claudin-5. We demonstrate that cARLA shifts the gene expressional profile of human stem cell–derived endothelial cells toward the in vivo brain endothelial signature, with a higher glycocalyx density and efflux pump activity, lower rates of endocytosis, and a characteristic endothelial response to proinflammatory cytokines. Finally, we illustrate how cARLA can improve the predictive value of human BBB models regarding the brain penetration of drugs and targeted nanoparticles. Due to its synergistic effect, high reproducibility, and ease of use, cARLA has the potential to advance drug development for the human brain by improving BBB models across laboratories.}, year = {2024}, eissn = {1091-6490}, orcid-numbers = {Walter, Fruzsina/0000-0001-8145-2823; Figueiredo, Ricardo/0000-0003-3024-1254; Vizsnyiczai, Gaszton/0000-0003-3245-3736; Jan, Jeng-Shiung/0000-0002-8379-404X; Gosselet, Fabien/0000-0002-0481-5026; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:34673907, title = {Lab-on-a-chip models of the blood-brain barrier: evolution, problems, perspectives}, url = {https://m2.mtmt.hu/api/publication/34673907}, author = {Deli, Mária Anna and Porkoláb, Gergő and Kincses, András and Mészáros, Mária and Szecskó, Anikó and Kocsis, Anna and Vigh, Judit Piroska and Valkai, Sándor and Veszelka, Szilvia and Walter, Fruzsina and Dér, András}, doi = {10.1039/d3lc00996c}, journal-iso = {LAB CHIP}, journal = {LAB ON A CHIP}, volume = {24}, unique-id = {34673907}, issn = {1473-0197}, year = {2024}, eissn = {1473-0189}, pages = {1030-1063}, orcid-numbers = {Deli, Mária Anna/0000-0001-6084-6524; Valkai, Sándor/0000-0001-8479-8141; Walter, Fruzsina/0000-0001-8145-2823} } @article{MTMT:33621088, title = {Targeting Human Endothelial Cells with Glutathione and Alanine Increases the Crossing of a Polypeptide Nanocarrier through a Blood–Brain Barrier Model and Entry to Human Brain Organoids}, url = {https://m2.mtmt.hu/api/publication/33621088}, author = {Mészáros, Mária and Phan, Thi Ha My and Vigh, Judit Piroska and Porkoláb, Gergő and Kocsis, Anna and Páli, Emese K. and Polgár, Tamás Ferenc and Walter, Fruzsina and Bolognin, Silvia and Schwamborn, Jens C. and Jan, Jeng-Shiung and Deli, Mária Anna and Veszelka, Szilvia}, doi = {10.3390/cells12030503}, journal-iso = {CELLS-BASEL}, journal = {CELLS}, volume = {12}, unique-id = {33621088}, abstract = {Nanoparticles (NPs) are the focus of research efforts that aim to develop successful drug delivery systems for the brain. Polypeptide nanocarriers are versatile platforms and combine high functionality with good biocompatibility and biodegradability. The key to the efficient brain delivery of NPs is the specific targeting of cerebral endothelial cells that form the blood–brain barrier (BBB). We have previously discovered that the combination of two different ligands of BBB nutrient transporters, alanine and glutathione, increases the permeability of vesicular NPs across the BBB. Our aim here was to investigate whether the combination of these molecules can also promote the efficient transfer of 3-armed poly(l-glutamic acid) NPs across a human endothelial cell and brain pericyte BBB co-culture model. Alanine and glutathione dual-targeted polypeptide NPs showed good cytocompatibility and elevated cellular uptake in a time-dependent and active manner. Targeted NPs had a higher permeability across the BBB model and could subsequently enter midbrain-like organoids derived from healthy and Parkinson’s disease patient-specific stem cells. These results indicate that poly(l-glutamic acid) NPs can be used as nanocarriers for nervous system application and that the right combination of molecules that target cerebral endothelial cells, in this case alanine and glutathione, can facilitate drug delivery to the brain.}, year = {2023}, eissn = {2073-4409}, orcid-numbers = {Walter, Fruzsina/0000-0001-8145-2823; Bolognin, Silvia/0000-0002-1399-2999; Jan, Jeng-Shiung/0000-0002-8379-404X; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:33272291, title = {Effects of Hydroxypropyl-Beta-Cyclodextrin on Cultured Brain Endothelial Cells}, url = {https://m2.mtmt.hu/api/publication/33272291}, author = {Veszelka, Szilvia and Mészáros, Mária and Porkoláb, Gergő and Rusznyák, Ágnes and Szászné Réti-Nagy, Katalin and Deli, Mária Anna and Vecsernyés, Miklós and Bácskay, Ildikó and Váradi, Judit and Fenyvesi, Ferenc}, doi = {10.3390/molecules27227738}, journal-iso = {MOLECULES}, journal = {MOLECULES}, volume = {27}, unique-id = {33272291}, issn = {1420-3049}, abstract = {The application of 2-hydroxypropyl-beta-cyclodextrin (HPBCD) in the treatment of the rare cholesterol and lipid storage disorder Niemann–Pick disease type C opened new perspectives in the development of an efficient therapy. Even if the systemic administration of HPBCD was found to be effective, its low permeability across the blood–brain barrier (BBB) limited the positive neurological effects. Nevertheless, the cellular interactions of HPBCD with brain capillary endothelial cells have not been investigated in detail. In this study, the cytotoxicity, permeability, and cellular internalization of HPBCD on primary rat and immortalized human (hCMEC/D3) brain capillary endothelial cells were investigated. HPBCD shows no cytotoxicity on endothelial cells up to 100 µM, measured by impedance kinetics. Using a fluorescent derivative of HPBCD (FITC-HPBCD) the permeability measurements reveal that on an in vitro triple co-culture BBB model, FITC-HPBCD has low permeability, 0.50 × 10−6 cm/s, while on hCMEC/D3 cell layers, the permeability is higher, 1.86 × 10−5 cm/s. FITC-HPBCD enters brain capillary endothelial cells, is detected in cytoplasmic vesicles and rarely localized in lysosomes. The cellular internalization of HPBCD at the BBB can help to develop new strategies for improved HPBCD effects after systemic administration.}, year = {2022}, eissn = {1420-3049}, orcid-numbers = {Rusznyák, Ágnes/0000-0002-8837-7499; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:33064300, title = {Cellular Therapy Using Epitope-Imprinted Composite Nanoparticles to Remove α-Synuclein from an In Vitro Model}, url = {https://m2.mtmt.hu/api/publication/33064300}, author = {Lee, Mei-Hwa and Jan, Jeng-Shiung and Thomas, James L. and Shih, Yuan-Pin and Li, Jin-An and Lin, Chien-Yu and Ooya, Tooru and Barna, Lilla and Mészáros, Mária and Harazin, András and Porkoláb, Gergő and Veszelka, Szilvia and Deli, Mária Anna and Lin, Hung-Yin}, doi = {10.3390/cells11162584}, journal-iso = {CELLS-BASEL}, journal = {CELLS}, volume = {11}, unique-id = {33064300}, abstract = {Several degenerative disorders of the central nervous system, including Parkinson’s disease (PD), are related to the pathological aggregation of proteins. Antibodies against toxic disease proteins, such as α-synuclein (SNCA), are therefore being developed as possible therapeutics. In this work, one peptide (YVGSKTKEGVVHGVA) from SNCA was used as the epitope to construct magnetic molecularly imprinted composite nanoparticles (MMIPs). These composite nanoparticles were characterized by dynamic light scattering (DLS), high-performance liquid chromatography (HPLC), isothermal titration calorimetry (ITC), Brunauer–Emmett–Teller (BET) analysis, and superconducting quantum interference device (SQUID) analysis. Finally, the viability of brain endothelial cells that were treated with MMIPs was measured, and the extraction of SNCA from CRISPR/dCas9a-activated HEK293T cells from the in vitro model system was demonstrated for the therapeutic application of MMIPs.}, year = {2022}, eissn = {2073-4409}, orcid-numbers = {Jan, Jeng-Shiung/0000-0002-8379-404X; Ooya, Tooru/0000-0001-7766-5455; Harazin, András/0000-0002-0904-5606; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:33057051, title = {Distinct Uptake Routes Participate in Silver Nanoparticle Engulfment by Earthworm and Human Immune Cells}, url = {https://m2.mtmt.hu/api/publication/33057051}, author = {Kokhanyuk, Bohdana and Bagóné Vántus, Viola and Radnai, Balázs and Vámos, Eszter and Kajner, Gyula and Galbács, Gábor and Telek, Elek and Mészáros, Mária and Deli, Mária Anna and Németh, Péter and Engelmann, Péter}, doi = {10.3390/nano12162818}, journal-iso = {NANOMATERIALS-BASEL}, journal = {NANOMATERIALS}, volume = {12}, unique-id = {33057051}, abstract = {The consequences of engineered silver nanoparticle (AgNP) exposure and cellular interaction with the immune system are poorly understood. The immunocytes of the Eisenia andrei earthworm are frequently applied in ecotoxicological studies and possess functional similarity to vertebrate macrophages. Hence, we characterized and compared the endocytosis mechanisms for the uptake of 75 nm AgNPs by earthworm coelomocytes, human THP-1 monocytes, and differentiated THP-1 (macrophage-like) cells. Our results indicate that microtubule-dependent, scavenger–receptor, and PI3K signaling-mediated macropinocytosis are utilized during AgNP engulfment by human THP-1 and differentiated THP-1 cells. However, earthworm coelomocytes employ actin-dependent phagocytosis during AgNPs uptake. In both human and earthworm immunocytes, AgNPs were located in the cytoplasm, within the endo-/lysosomes. We detected that the internalization of AgNPs is TLR/MyD88-dependent, also involving the bactericidal/permeability-increasing protein (BPI) in the case of human immunocytes. The exposure led to decreased mitochondrial respiration in human immunocytes; however, in coelomocytes, it enhanced respiratory parameters. Our findings provide more data about NP trafficking as nano-carriers in the nanomedicine field, as well as contribute to an understanding of the ecotoxicological consequences of nanoparticle exposure.}, year = {2022}, eissn = {2079-4991}, orcid-numbers = {Vámos, Eszter/0000-0003-0622-442X; Galbács, Gábor/0000-0002-1799-5329; Telek, Elek/0000-0003-0396-4799; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:32575627, title = {A Triple Combination of Targeting Ligands Increases the Penetration of Nanoparticles across a Blood-Brain Barrier Culture Model}, url = {https://m2.mtmt.hu/api/publication/32575627}, author = {Veszelka, Szilvia and Mészáros, Mária and Porkoláb, Gergő and Szecskó, Anikó and Kondor, Nóra and Ferenc, Györgyi and Polgár, Tamás Ferenc and Katona, Gábor and Kóta, Zoltán and Kelemen, Lóránd and Páli, Tibor and Vigh, Judit Piroska and Walter, Fruzsina and Bolognin, Silvia and Schwamborn, Jens C. and Jan, Jeng-Shiung and Deli, Mária Anna}, doi = {10.3390/pharmaceutics14010086}, journal-iso = {PHARMACEUTICS}, journal = {PHARMACEUTICS}, volume = {14}, unique-id = {32575627}, issn = {1999-4923}, year = {2022}, eissn = {1999-4923}, orcid-numbers = {Ferenc, Györgyi/0000-0002-3456-319X; Katona, Gábor/0000-0003-1564-4813; Kóta, Zoltán/0000-0003-2420-8773; Kelemen, Lóránd/0000-0001-7772-2165; Páli, Tibor/0000-0003-1649-1097; Walter, Fruzsina/0000-0001-8145-2823; Bolognin, Silvia/0000-0002-1399-2999; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:32491017, title = {S1R agonist modulates rat platelet eicosanoid synthesis and aggregation}, url = {https://m2.mtmt.hu/api/publication/32491017}, author = {Váczi, Sándor and Barna, Lilla and Harazin, András and Mészáros, Mária and Porkoláb, Gergő and Zvara, Ágnes and Ónody, Rita and Földesi, Imre and Veszelka, Szilvia and Penke, Botond and Fülöp, Lívia and Deli, Mária Anna and Mezei, Zsófia}, doi = {10.1080/09537104.2021.1981843}, journal-iso = {PLATELETS}, journal = {PLATELETS}, volume = {33}, unique-id = {32491017}, issn = {0953-7104}, abstract = {Sigma-1 receptor (S1R) is detected in different cell types and can regulate intracellular signaling pathways. S1R plays a role in the pathomechanism of diseases and the regulation of neurotransmitters. Fluvoxamine can bind to S1R and reduce the serotonin uptake of neurons and platelets. We therefore hypothesized that platelets express S1R, which can modify platelet function. The expression of the SIGMAR1 gene in rat platelets was examined with a reverse transcription polymerase chain reaction and a quantitative polymerase chain reaction. The receptor was also visualized by immunostaining and confocal laser scanning microscopy. The effect of S1R agonist PRE-084 on the eicosanoid synthesis of isolated rat platelets and ADP- and AA-induced platelet aggregation was examined. S1R was detected in rat platelets both at gene and protein levels. Pretreatment with PRE-084 of resting platelets induced elevation of eicosanoid synthesis. The rate of elevation in thromboxane B2 and prostaglandin D2 synthesis was similar, but the production of prostaglandin E2 was higher. The concentration-response curve showed a sigmoidal form. The most effective concentration of the agonist was 2 µM. PRE-084 increased the quantity of cyclooxygenase-1 as detected by ELISA. PRE-084 also elevated the ADP- and AA-induced platelet aggregation. S1R of platelets might regulate physiological or pathological functions. © 2021 Taylor & Francis Group, LLC.}, keywords = {AGGREGATION; PLATELETS; Sigma-1 receptor; Eicosanoid; PRE-084}, year = {2022}, eissn = {1369-1635}, pages = {709-718}, orcid-numbers = {Váczi, Sándor/0000-0002-9642-7126; Harazin, András/0000-0002-0904-5606; Földesi, Imre/0000-0002-3329-8136; Penke, Botond/0000-0003-0938-0567; Fülöp, Lívia/0000-0002-8010-0129; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:32531953, title = {In Vitro Comparative Study of Solid Lipid and PLGA Nanoparticles Designed to Facilitate Nose-to-Brain Delivery of Insulin}, url = {https://m2.mtmt.hu/api/publication/32531953}, author = {Akel, Hussein and Pannonhalminé Csóka, Ildikó and Ambrus, Rita and Bocsik, Alexandra and Gróf, Ilona and Mészáros, Mária and Szecskó, Anikó and Kozma, Gábor and Veszelka, Szilvia and Deli, Mária Anna and Kónya, Zoltán and Katona, Gábor}, doi = {10.3390/ijms222413258}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {22}, unique-id = {32531953}, issn = {1661-6596}, year = {2021}, eissn = {1422-0067}, orcid-numbers = {Pannonhalminé Csóka, Ildikó/0000-0003-0807-2781; Kozma, Gábor/0000-0003-2033-0720; Deli, Mária Anna/0000-0001-6084-6524; Kónya, Zoltán/0000-0002-9406-8596; Katona, Gábor/0000-0003-1564-4813} } @article{MTMT:32156859, title = {Optically Manipulated Microtools to Measure Adhesion of the Nanoparticle-Targeting Ligand Glutathione to Brain Endothelial Cells}, url = {https://m2.mtmt.hu/api/publication/32156859}, author = {Fekete, Tamás and Mészáros, Mária and Szegletes, Zsolt and Vizsnyiczai, Gaszton and Zimányi, László and Deli, Mária Anna and Veszelka, Szilvia and Kelemen, Lóránd}, doi = {10.1021/acsami.1c08454}, journal-iso = {ACS APPL MATER INTER}, journal = {ACS APPLIED MATERIALS & INTERFACES}, volume = {13}, unique-id = {32156859}, issn = {1944-8244}, year = {2021}, eissn = {1944-8252}, pages = {39018-39029}, orcid-numbers = {Fekete, Tamás/0000-0002-1557-845X; Szegletes, Zsolt/0000-0003-2202-6933; Vizsnyiczai, Gaszton/0000-0003-3245-3736; Zimányi, László/0000-0002-5101-2023; Deli, Mária Anna/0000-0001-6084-6524; Kelemen, Lóránd/0000-0001-7772-2165} }