Browsing by Author "Polakovicova, Iva"

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    Angiotensin-(1-9) prevents cardiomyocyte hypertrophy by controlling mitochondrial dynamics via miR-129-3p/PKIA pathway
    (2020) Sotomayor-Flores, C.; Rivera-Mejias, P.; Vasquez-Trincado, C.; Lopez-Crisosto, C.; Morales, P. E.; Pennanen, C.; Polakovicova, Iva; Roa Strauch, Juan Carlos Enrique; Ocaranza, María Paz; Corvalán R., Alejandro; Aliaga-Tobar, V.; Garcia, L.; Rothermel, B. A.; Maracaja-Coutinho, V.; Ho-Xuan, H.; Meister, G.; Chiong, M.; Parra, V.; Lavandero, S.
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    Correction to : MicroRNA‑335‑5p is a potential suppressor of metastasis and invasion in gastric cancer
    (2021) Sandoval Bórquez, Alejandra; Polakovicova, Iva; Carrasco Véliz, Nicolás; Lobos González, Lorena; Riquelme, Ismael; Carrasco Avino, Gonzalo; Bizama, Carolina; Norero Muñoz, Enrique; Owen, Gareth Ivor; Roa Strauch, Juan Carlos Enrique; Corvalán R., Alejandro
    An amendment to this paper has been published and can be accessed via the original article.
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    Extracellular vesicles through the blood–brain barrier: a review
    (2022) Ramos Zaldívar, Héctor M.; Polakovicova, Iva; Salas-Huenuleo, Edison; Corvalán R., Alejandro; Kogan, Marcelo J.; Yefi Rubio, Claudia Pamela; Andía Kohnenkampf, Marcelo Edgardo
    Extracellular vesicles (EVs) are particles naturally released from cells that are delimited by a lipid bilayer and are unable to replicate. How the EVs cross the Blood–Brain barrier (BBB) in a bidirectional manner between the bloodstream and brain parenchyma remains poorly understood. Most in vitro models that have evaluated this event have relied on monolayer transwell or microfluidic organ-on-a-chip techniques that do not account for the combined effect of all cellular layers that constitute the BBB at different sites of the Central Nervous System. There has not been direct transcytosis visualization through the BBB in mammals in vivo, and evidence comes from in vivo experiments in zebrafish. Literature is scarce on this topic, and techniques describing the mechanisms of EVs motion through the BBB are inconsistent. This review will focus on in vitro and in vivo methodologies used to evaluate EVs transcytosis, how EVs overcome this fundamental structure, and discuss potential methodological approaches for future analyses to clarify these issues. Understanding how EVs cross the BBB will be essential for their future use as vehicles in pharmacology and therapeutics.
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    Gold nanoparticle based double-labeling of melanoma extracellular vesicles to determine the specificity of uptake by cells and preferential accumulation in small metastatic lung tumors
    (2020) Lara, Pablo.; Polakovicova, Iva; Corvalán R., Alejandro; Palma‑Florez, Sujey.; Salas-Huenuleo, Edison.; Guerrero, Simón.; Lobos González, Lorena.; Campos, América.; Muñoz Anrique, Luis.; Jorquera‑Cordero, Carla.
    Abstract Background Extracellular vesicles (EVs) have shown great potential for targeted therapy, as they have a natural ability to pass through biological barriers and, depending on their origin, can preferentially accumulate at defined sites, including tumors. Analyzing the potential of EVs to target specific cells remains challenging, considering the unspecific binding of lipophilic tracers to other proteins, the limitations of fluorescence for deep tissue imaging and the effect of external labeling strategies on their natural tropism. In this work, we determined the cell-type specific tropism of B16F10-EVs towards cancer cell and metastatic tumors by using fluorescence analysis and quantitative gold labeling measurements. Surface functionalization of plasmonic gold nanoparticles was used to promote indirect labeling of EVs without affecting size distribution, polydispersity, surface charge, protein markers, cell uptake or in vivo biodistribution. Double-labeled EVs with gold and fluorescent dyes were injected into animals developing metastatic lung nodules and analyzed by fluorescence/computer tomography imaging, quantitative neutron activation analysis and gold-enhanced optical microscopy. Results We determined that B16F10 cells preferentially take up their own EVs, when compared with colon adenocarcinoma, macrophage and kidney cell-derived EVs. In addition, we were able to detect the preferential accumulation of B16F10 EVs in small metastatic tumors located in lungs when compared with the rest of the organs, as well as their precise distribution between tumor vessels, alveolus and tumor nodules by histological analysis. Finally, we observed that tumor EVs can be used as effective vectors to increase gold nanoparticle delivery towards metastatic nodules. Conclusions Our findings provide a valuable tool to study the distribution and interaction of EVs in mice and a novel strategy to improve the targeting of gold nanoparticles to cancer cells and metastatic nodules by using the natural properties of malignant EVs.Abstract Background Extracellular vesicles (EVs) have shown great potential for targeted therapy, as they have a natural ability to pass through biological barriers and, depending on their origin, can preferentially accumulate at defined sites, including tumors. Analyzing the potential of EVs to target specific cells remains challenging, considering the unspecific binding of lipophilic tracers to other proteins, the limitations of fluorescence for deep tissue imaging and the effect of external labeling strategies on their natural tropism. In this work, we determined the cell-type specific tropism of B16F10-EVs towards cancer cell and metastatic tumors by using fluorescence analysis and quantitative gold labeling measurements. Surface functionalization of plasmonic gold nanoparticles was used to promote indirect labeling of EVs without affecting size distribution, polydispersity, surface charge, protein markers, cell uptake or in vivo biodistribution. Double-labeled EVs with gold and fluorescent dyes were injected into animals developing metastatic lung nodules and analyzed by fluorescence/computer tomography imaging, quantitative neutron activation analysis and gold-enhanced optical microscopy. Results We determined that B16F10 cells preferentially take up their own EVs, when compared with colon adenocarcinoma, macrophage and kidney cell-derived EVs. In addition, we were able to detect the preferential accumulation of B16F10 EVs in small metastatic tumors located in lungs when compared with the rest of the organs, as well as their precise distribution between tumor vessels, alveolus and tumor nodules by histological analysis. Finally, we observed that tumor EVs can be used as effective vectors to increase gold nanoparticle delivery towards metastatic nodules. Conclusions Our findings provide a valuable tool to study the distribution and interaction of EVs in mice and a novel strategy to improve the targeting of gold nanoparticles to cancer cells and metastatic nodules by using the natural properties of malignant EVs.
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    Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines
    (2018) Thery, Clotilde; Witwer, Kenneth W.; Aikawa, Elena; Jose Alcaraz, Maria; Anderson, Johnathon D.; Andriantsitohaina, Ramaroson; Antoniou, Anna; Arab, Tanina; Archer, Fabienne; Atkin-Smith, Georgia K.; Ayre, D. Craig; Bach, Jean-Marie; Bachurski, Daniel; Baharvand, Hossein; Balaj, Leonora; Baldacchino, Shawn; Bauer, Natalie N.; Baxter, Amy A.; Bebawy, Mary; Beckham, Carla; Zavec, Apolonija Bedina; Benmoussa, Abderrahim; Berardi, Anna C.; Bergese, Paolo; Bielska, Ewa; Blenkiron, Cherie; Bobis-Wozowicz, Sylwia; Boilard, Eric; Boireau, Wilfrid; Bongiovanni, Antonella; Borras, Francesc E.; Bosch, Steffi; Boulanger, Chantal M.; Breakefield, Xandra; Breglio, Andrew M.; Brennan, Meadhbh A.; Brigstock, David R.; Brisson, Alain; Broekman, Marike L. D.; Bromberg, Jacqueline F.; Bryl-Gorecka, Paulina; Buch, Shilpa; Buck, Amy H.; Burger, Dylan; Busatto, Sara; Buschmann, Dominik; Bussolati, Benedetta; Buzas, Edit, I; Byrd, James Bryan; Camussi, Giovanni; Carter, David R. F.; Caruso, Sarah; Chamley, Lawrence W.; Chang, Yu-Ting; Chen, Chihchen; Chen, Shuai; Cheng, Lesley; Chin, Andrew R.; Clayton, Aled; Clerici, Stefano P.; Cocks, Alex; Cocucci, Emanuele; Coffey, Robert J.; Cordeiro-da-Silva, Anabela; Couch, Yvonne; Coumans, Frank A. W.; Coyle, Beth; Crescitelli, Rossella; Criado, Miria Ferreira; D'Souza-Schorey, Crislyn; Das, Saumya; Chaudhuri, Amrita Datta; de Candia, Paola; De Santana Junior, Eliezer F.; De Wever, Olivier; del Portillo, Hernando A.; Demaret, Tanguy; Deville, Sarah; Devitt, Andrew; Dhondt, Bert; Di Vizio, Dolores; Dieterich, Lothar C.; Dolo, Vincenza; Dominguez Rubio, Ana Paula; Dominici, Massimo; Dourado, Mauricio R.; Driedonks, Tom A. P.; Duarte, Filipe, V; Duncan, Heather M.; Eichenberger, Ramon M.; Ekstrom, Karin; Andaloussi, Samir E. L.; Elie-Caille, Celine; Erdbrugger, Uta; Falcon-Perez, Juan M.; Fatima, Farah; Fish, Jason E.; Flores-Bellver, Miguel; Forsonits, Andras; Frelet-Barrand, Annie; Fricke, Fabia; Fuhrmann, Gregor; Gabrielsson, Susanne; Gamez-Valero, Ana; Gardiner, Chris; Gaertner, Kathrin; Gaudin, Raphael; Gho, Yong Song; Giebel, Bernd; Gilbert, Caroline; Gimona, Mario; Giusti, Ilaria; Goberdhan, Deborah C., I; Goergens, Andre; Gorski, Sharon M.; Greening, David W.; Gross, Julia Christina; Gualerzi, Alice; Gupta, Gopal N.; Gustafson, Dakota; Handberg, Aase; Haraszti, Reka A.; Harrison, Paul; Hegyesi, Hargita; Hendrix, An; Hill, Andrew F.; Hochberg, Fred H.; Hoffmann, Karl F.; Holder, Beth; Holthofer, Harry; Hosseinkhani, Baharak; Hu, Guoku; Huang, Yiyao; Huber, Veronica; Hunt, Stuart; Ibrahim, Ahmed Gamal-Eldin; Ikezu, Tsuneya; Inal, Jameel M.; Isin, Mustafa; Ivanova, Alena; Jackson, Hannah K.; Jacobsen, Soren; Jay, Steven M.; Jayachandran, Muthuvel; Jenster, Guido; Jiang, Lanzhou; Johnson, Suzanne M.; Jones, Jennifer C.; Jong, Ambrose; Jovanovic-Talisman, Tijana; Jung, Stephanie; Kalluri, Raghu; Kano, Shin-ichi; Kaur, Sukhbir; Kawamura, Yumi; Keller, Evan T.; Khamari, Delaram; Khomyakova, Elena; Khvorova, Anastasia; Kierulf, Peter; Kim, Kwang Pyo; Kislinger, Thomas; Klingeborn, Mikael; Klinke, David J., II; Kornek, Miroslaw; Kosanovic, Maja M.; Kovacs, Arpad Ferenc; Kraemer-Albers, Eva-Maria; Krasemann, Susanne; Krause, Mirja; Kurochkin, Igor, V; Kusuma, Gina D.; Kuypers, Soren; Laitinen, Saara; Langevin, Scott M.; Languino, Lucia R.; Lannigan, Joanne; Lasser, Cecilia; Laurent, Louise C.; Lavieu, Gregory; Lazaro-Ibanez, Elisa; Le Lay, Soazig; Lee, Myung-Shin; Lee, Yi Xin Fiona; Lemos, Debora S.; Lenassi, Metka; Leszczynska, Aleksandra; Li, Isaac T. S.; Liao, Ke; Libregts, Sten F.; Ligeti, Erzsebet; Lim, Rebecca; Lim, Sai Kiang; Line, Aija; Linnemannstoens, Karen; Llorente, Alicia; Lombard, Catherine A.; Lorenowicz, Magdalena J.; Lorincz, Akos M.; Lotvall, Jan; Lovett, Jason; Lowry, Michelle C.; Loyer, Xavier; Lu, Quan; Lukomska, Barbara; Lunavat, Taral R.; Maas, Sybren L. N.; Malhi, Harmeet; Marcilla, Antonio; Mariani, Jacopo; Mariscal, Javier; Martens-Uzunova, Elena S.; Martin-Jaular, Lorena; Martinez, M. Carmen; Martins, Vilma Regina; Mathieu, Mathilde; Mathivanan, Suresh; Maugeri, Marco; McGinnis, Lynda K.; McVey, Mark J.; Meckes, David G., Jr.; Meehan, Katie L.; Mertens, Inge; Minciacchi, Valentina R.; Moller, Andreas; Jorgensen, Malene Moller; Morales-Kastresana, Aizea; Morhayim, Jess; Mullier, Francois; Muraca, Maurizio; Musante, Luca; Mussack, Veronika; Muth, Dillon C.; Myburgh, Kathryn H.; Najrana, Tanbir; Nawaz, Muhammad; Nazarenko, Irina; Nejsum, Peter; Neri, Christian; Neri, Tommaso; Nieuwland, Rienk; Nimrichter, Leonardo; Nolan, John P.; Nolte-'t Hoen, Esther N. M.; Noren Hooten, Nicole; O'Driscoll, Lorraine; O'Grady, Tina; O'Loghlen, Ana; Ochiya, Takahiro; Olivier, Martin; Ortiz, Alberto; Ortiz, Luis A.; Osteikoetxea, Xabier; Ostegaard, Ole; Ostrowski, Matias; Park, Jaesung; Pegtel, D. Michiel; Peinado, Hector; Perut, Francesca; Pfaffl, Michael W.; Phinney, Donald G.; Pieters, Bartijn C. H.; Pink, Ryan C.; Pisetsky, David S.; von Strandmann, Elke Pogge; Polakovicova, Iva; Poon, Ivan K. H.; Powell, Bonita H.; Prada, Ilaria; Pulliam, Lynn; Quesenberry, Peter; Radeghieri, Annalisa; Raffai, Robert L.; Raimondo, Stefania; Rak, Janusz; Ramirez, Marcel, I; Raposo, Graca; Rayyan, Morsi S.; Regev-Rudzki, Neta; Ricklefs, Franz L.; Robbins, Paul D.; Roberts, David D.; Rodrigues, Silvia C.; Rohde, Eva; Rome, Sophie; Rouschop, Kasper M. A.; Rughetti, Aurelia; Russell, Ashley E.; Saa, Paula; Sahoo, Susmita; Salas-Huenuleo, Edison; Sanchez, Catherine; Saugstad, Julie A.; Saul, Meike J.; Schiffelers, Raymond M.; Schneider, Raphael; Schoyen, Tine Hiorth; Scott, Aaron; Shahaj, Eriomina; Sharma, Shivani; Shatnyeva, Olga; Shekari, Faezeh; Shelke, Ganesh Vilas; Shetty, Ashok K.; Shiba, Kiyotaka; Siljander, Pia R-M; Silva, Andreia M.; Skowronek, Agata; Snyder, Orman L., II; Soares, Rodrigo Pedro; Sodar, Barbara W.; Soekmadji, Carolina; Sotillo, Javier; Stahl, Philip D.; Stoorvogel, Willem; Stott, Shannon L.; Strasser, Erwin F.; Swift, Simon; Tahara, Hidetoshi; Tewari, Muneesh; Timms, Kate; Tiwari, Swasti; Tixeira, Rochelle; Tkach, Mercedes; Toh, Wei Seong; Tomasini, Richard; Torrecilhas, Ana Claudia; Pablo Tosar, Juan; Toxavidis, Vasilis; Urbanelli, Lorena; Vader, Pieter; van Balkom, Bas W. M.; van der Grein, Susanne G.; Van Deun, Jan; van Herwijnen, Martijn J. C.; Van Keuren-Jensen, Kendall; van Niel, Guillaume; van Royen, Martin E.; van Wijnen, Andre J.; Helena Vasconcelos, M.; Vechetti, Ivan J., Jr.; Veit, Tiago D.; Vella, Laura J.; Velot, Emilie; Verweij, Frederik J.; Vestad, Beate; Vinas, Jose L.; Visnovitz, Tamas; Vukman, Krisztina V.; Wahlgren, Jessica; Watson, Dionysios C.; Wauben, Marca H. M.; Weaver, Alissa; Webber, Jason P.; Weber, Viktoria; Wehman, Ann M.; Weiss, Daniel J.; Welsh, Joshua A.; Wendt, Sebastian; Wheelock, Asa M.; Wiener, Zoltan; Witte, Leonie; Wolfram, Joy; Xagorari, Angeliki; Xander, Patricia; Xu, Jing; Yan, Xiaomei; Yanez-Mo, Maria; Yin, Hang; Yuana, Yuana; Zappulli, Valentina; Zarubova, Jana; Zekas, Vytautas; Zhang, Jian-ye; Zhao, Zezhou; Zheng, Lei; Zheutlin, Alexander R.; Zickler, Antje M.; Zimmermann, Pascale; Zivkovic, Angela M.; Zocco, Davide; Zuba-Surma, Ewa K.
    The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles ("MISEV") guidelines for the field in 2014. We now update these "MISEV2014" guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
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    Peptide Targeted Gold Nanoplatform Carrying miR-145 Induces Antitumoral Effects in Ovarian Cancer Cells
    (2022) Salas-Huenuleo, Edison; Hernandez, Andrea; Lobos-Gonzalez, Lorena; Polakovicova, Iva; Morales-Zavala, Francisco; Araya, Eyleen; Celis, Freddy; Romero, Carmen; Kogan, Marcelo J.
    One of the recent attractive therapeutic approaches for cancer treatment is restoring downregulated microRNAs. They play an essential muti-regulatory role in cellular processes such as proliferation, differentiation, survival, apoptosis, cell cycle, angiogenesis, and metastasis, among others. In this study, a gold nanoplatform (GNPF) carrying miR-145, a downregulated microRNA in many cancer types, including epithelial ovarian cancer, was designed and synthesized. For targeting purposes, the GNPF was functionalized with the FSH33 peptide, which provided selectivity for ovarian cancer, and loaded with the miR-145 to obtain the nanosystem GNPF-miR-145. The GNPF-mir-145 was selectively incorporated in A2780 and SKOV3 cells and significantly inhibited cell viability and migration and exhibited proliferative and anchor-independent growth capacities. Moreover, it diminished VEGF release and reduced the spheroid size of ovarian cancer through the damage of cell membranes, thus decreasing cell viability and possibly activating apoptosis. These results provide important advances in developing miR-based therapies using nanoparticles as selective vectors and provide approaches for in vivo evaluation.
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    The Cervical and Meningeal Lymphatic Network as a Pathway for Retrograde Nanoparticle Transport to the Brain
    (2024) Ramos-Zaldivar, Hector; Polakovicova, Iva; Salas-Huenuleo, Edison; Yefi, Claudia P.; Silva-Ancahuail, David; Jara-Guajardo, Pedro; Oyarzun, Juan Esteban; Neira-Troncoso, Alvaro; Burgos, Patricia, V; Cavieres, Viviana A.; Arias-Munoz, Eloisa; Martinez, Carlos; Riveros, Ana L.; Corvalan, Alejandro H.; Kogan, Marcelo J.; Andia, Marcelo E.
    Introduction: The meningeal lymphatic vessels have been described as a pathway that transports cerebrospinal fluid and interstitial fluid in a unidirectional manner towards the deep cervical lymph nodes. However, these vessels exhibit anatomical and molecular characteristics typical of initial lymphatic vessels, with the absence of surrounding smooth muscle and few or absent valves. Given its structure, this network could theoretically allow for bidirectional motion. Nevertheless, it has not been assessed as a potential route for nanoparticles to travel from peripheral tissues to the brain. Methods: We employed superparamagnetic iron oxide nanoparticles (SPIONs), exosomes loaded with SPIONs, gold nanorods, and Chinese ink nanoparticles. SPIONs were prepared via chemical coprecipitation, while exosomes were isolated from the B16F10 melanoma cell line through the Exo-Spin column protocol and loaded with SPIONs through electroporation. Gold nanorods were functionalized with polyethylene glycol. We utilized C57BL/6 mice for post-mortem and in vivo procedures. To evaluate the retrograde directional flow, we injected each nanoparticle solution in the deep cervical lymph node. The head and neck were fixed for magnetic resonance imaging and histological analysis. Results: Here we show that extracellular vesicles derived from the B16F10 melanoma cell line, along with superparamagnetic iron oxide nanoparticles, gold nanorods, and Chinese ink nanoparticles can reach the meningeal lymphatic vessels and the brain of C57BL/6 mice after administration within the deep cervical lymph nodes post-mortem and in vivo, exclusively through lymphatic structures. Discussion: The functional anatomy of dural lymphatics has been found to be conserved between mice and humans, suggesting that our findings may have significant implications for advancing targeted drug delivery systems using nanoparticles. Understanding the retrograde transport of nanoparticles through the meningeal lymphatic network could lead to novel therapeutic approaches in nanomedicine, offering new insights into fluid dynamics in both physiological and neuropathological contexts. Further research into this pathway may unlock new strategies for treating neurological diseases or enhancing drug delivery to the brain.
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    The Phylogeographic Diversity of EBV and Admixed Ancestry in the Americas-Another Model of Disrupted Human-Pathogen Co-Evolution
    (2019) Corvalán Rodríguez, Alejandro; Ruedlinger, Jenny; Mayo, Tomás de; Polakovicova, Iva; González-Hormázabal, Patricio; Aguayo, Francisco
    Epstein-Barr virus (EBV) is an etiological agent for gastric cancer with significant worldwide variations. Molecular characterizations of EBV have shown phylogeographical variations among healthy populations and in EBV-associated diseases, articularly the cosegregated BamHI-I fragment and XhoI restriction site of exon 1 of the LMP-1 gene. In the Americas, both cosegregated variants are present in EBV carriers, which aligns with the history of Asian and European human migration to this continent. Furthermore, novel recombinant variants have been found, reflecting the genetic makeup of this continent. However, in the case of EBV-associated gastric cancer (EBV-associated GC), the cosegregated European BamHI-“i” fragment and XhoI restriction site strain prevails. Thus, we propose that a disrupted coevolution between viral phylogeographical strains and mixed human ancestry in the Americas might explain the high prevalence of this particular gastric cancer subtype. This cosegregated region contains two relevant transcripts for EBV-associated GC, the BARF-1 and miR-BARTs. Thus, genome-wide association studies (GWAS) or targeted sequencing of both transcripts may be required to clarify their role as a potential source of this disrupted coevolution.