Mecanismos de acción antitumoral de compuestos fitoactivos y su nanovehiculización como estrategia para generar sistemas terapéuticos con propiedades mejoradas

Grupo de trabajo

Director de LíneaRodenak Kladniew

Rodenak Kladniew, Boris

Investigador
brodenak@med.unlp.edu.ar

Castro, María Agustina Castro

Becaria
magustinacg@med.unlp.edu.ar

Colaboradores de otras instituciones

Stephan, Gehring
Johannes Gutenberg-Universität Mainz, Germany.

Stärkel, Peter
Laboratory of Gastroenterology, Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium.

Chain, Yamil
Instituto de Investigaciones Fisico-Quimicas Teoricas y Aplicadas . INIFTA - UNLP - CCT La Plata

León, Ignacio
Centro de Química Inorgánica "Dr. Pedro J. Aymonino" . CEQUINOR - UNLP - CCT La Plata

Islan, German A.
Centro de Investigación y Desarrollo en Fermentaciones Industriales. CINDEFI - Facultad de Ciencias Exactas - UNLP.

Resumen de línea

La naturaleza es una excelente fuente de moléculas con actividad farmacológica. En búsqueda de alternativas terapéuticas que permitan reemplazar o complementar las terapias actuales, en los últimos años ha resurgido con gran entusiasmo el estudio de compuestos naturales como fuente de nuevas drogas.
Compuestos derivados de plantas como flavonoides, polifenoles y terpenos han demostrado numerosas propiedades farmacológicas entre las que se destacan su actividad quimiopreventiva y quimioterapéutica. Su empleo como fitofármacos ha cobrado un enorme interés considerando su origen natural, amplia disponibilidad, bajo costo, alto potencial terapéutico y ausencia de efectos tóxicos en relación con los fármacos convencionales disponibles. A pesar de su enorme potencial, su utilización presenta limitaciones relacionadas a su baja solubilidad, estabilidad, volatilidad y reducida biodisponibilidad que deben ser resueltas para mejorar su efectividad.
En este contexto, la nanotecnología aparece como una herramienta potente para superar las limitaciones relacionadas a la solubilidad, estabilidad, metabolismo e inespecificidad de acción de moléculas con actividad farmacológica. El desarrollo de nanopartículas capaces de co-encapsular drogas quimioterapéuticas y compuestos naturales con actividad antitumoral y transportarlos selectivamente hacia células tumorales surge como una alternativa terapéutica superadora a los tratamientos actuales.
Los objetivos generales de este proyecto proponen evaluar la actividad antitumoral y mecanismos de acción de fitocompuestos en modelos in vitro 2D y 3D. Diseñar, caracterizar y evaluar in vitro nanopartículas híbridas bioactivas conteniendo fitocompuestos que sirvan como sistemas terapéuticos de bajo costo para el transporte selectivo y actividad potenciada de drogas antineoplásicas.

Cytotoxic Screening and Enhanced Anticancer Activity of Lippia alba and Clinopodium nepeta Essential Oils-Loaded Biocompatible Lipid Nanoparticles against Lung and Colon Cancer Cells.
Rodenak-Kladniew, B; Castro, M. A; Gambaro, R. C; Girotti, J; Cisneros, J. S; Viña, S; Islan, G. A.
2023. Pharmaceutics, 15(8), 2045
DOI: 10.3390/pharmaceutics15082045

Enhanced anticancer activity of encapsulated geraniol into biocompatible lipid nanoparticles against A549 human lung cancer cells.
Rodenak-Kladniew, B; Gambaro, R; Cisneros, J. S; Huck-Iriart, C; Padula, G; Castro, G. R; Islan, G. A.
2023. Journal of Drug Delivery Science and Technology, 80, 104159
DOI:10.1016/j.jddst.2023.104159

In vitro evaluation of antiatherogenic potential of Origanum× paniculatum, Lippia alba, Clinopodium nepeta, and Eucalyptus globulus essential oils.
Castro, M. A; Girotti, J. R; Dumrauf, B; Rodenak-Kladniew, B; Zaro, M. J; Otero, C. M; Crespo, R.
2023. Journal of Herbal Medicine, 42, 100785
DOI: 10.1016/j.hermed.2023.100785

Pectin-based inks development for 3D bioprinting of scaffolds.
Passamai, V. E; Katz, S; Rodenak-Kladniew, B; Alvarez, V; Castro, G. R.
2023. Journal of Polymer Research, 30(1), 35
DOI: 10.1007/s10965-022-03402-x

Prodigiosin: a promising biomolecule with many potential biomedical applications.
Islan, German A.; Rodenak-Kladniew, Boris; Noacco, Nehuen; Duran, Nelson; Castro, Guillermo R.
2022. Bioengineered. , Londres: Taylor & Francis, 2022 - . vol. 13, n° 6, p. 14227-14258. ISSN 2165-5979
doi.org/10.1080/21655979.2022.2084498

Enzymatic Active Release of Violacein Present in Nanostructured Lipid Carrier by Lipase Encapsulated in 3D-Bioprinted Chitosan-Hydroxypropyl Methylcellulose Matrix With Anticancer Activity.
Rivero Berti, Ignacio; Rodenak-Kladniew, Boris E.; Katz, Sergio F.; Arrua, Eva Carolina; Alvarez, Vera A.; Duran, Nelson; Castro, Guillermo R.
2022. Frontiers in chemistry. , Lausanne: Frontiers Media S.A. vol. 10, p. 914126-914138
doi.org/10.3389/fchem.2022.914126

Design of magnetic hybrid nanostructured lipid carriers containing 1, 8-cineole as delivery systems for anticancer drugs: Physicochemical and cytotoxic studies.
Rodenak-Kladniew, B; Noacco, N; de Berti, I. P; Stewart, S. J; Cabrera, A. F; Alvarez, V. A; Islan, G. A.
2021.Colloids and Surfaces B: Biointerfaces, 202, 111710
doi.org/10.1016/j.colsurfb.2021.111710

Silver nanoparticle filter for domestic wastewater reuse.
Gagneten, A. M; Romero, N; Reno, U; Regaldo, L; Kergaravat, S. V; Rodenak‐Kladniew, B. E; Castro, G. R.
2021. Journal of Chemical Technology & Biotechnology.
doi.org/10.1002/jctb.6710

Citrus reticulata peel oil as an antiatherogenic agent: Hypolipogenic effect in hepatic cells, lipid storage decrease in foam cells, and prevention of LDL oxidation.
Castro, María A.; Llanos, Manuel A.; Rodenak-Kladniew, Boris E.; Gavernet, Luciana; Galle, Marianela E.; Crespo, Rosana.
2020. Nutrition metabolism and cardiovascular diseases: ELSEVIER SCI LTD, vol. 30, n° 9, p. 1590-1599. ISSN 0939-4753
doi.org/10.1016/j.numecd.2020.04.033

Anti-cancer mechanisms of linalool and 1,8-cineole in non-small cell lung cancer A549 cells.
Rodenak-Kladniew, Boris; Castro, María Agustina; Crespo, Rosana; Galle, Marianela; García De Bravo, Margarita.
2020. Heliyon: Elsevier Ltd, vol. 6, n° 12, p. 1-13. ISSN 2405-8440
doi.org/10.1016/j.heliyon.2020.e05639

Assessment of: In vitro cytotoxicity of imidazole ionic liquids and inclusion in targeted drug carriers containing violacein.
Rivero Berti, Ignacio; Rodenak-Kladniew, Boris; Onaindia, Celeste; Adam, Claudia G.; Islan, German A.; Durán, Nelson; Castro, Guillermo R.
2020. Rsc advances: Royal Society of Chemistry. vol. 10, n° 49, p. 29336-29346.
doi.org/10.1039/D0RA05101B

Antimicrobial activities of bacterial cellulose – Silver montmorillonite nanocomposites for wound healing
Horue, Manuel; Cacicedo, Maximiliano L; Fernández, Mariela A; Rodenak-Kladniew, Boris; Torres Sánchez, Rosa M; Castro, Guillermo R.
2020. Amsterdam: ELSEVIER SCIENCE BV, vol. 116, p. 1-11. ISSN 0928-4931
doi.org/10.1016/j.msec.2020.111152

1, 8-Cineole promotes G0/G1 cell cycle arrest and oxidative stress-induced senescence in HepG2 cells and sensitizes cells to anti-senescence drugs.
Rodenak-Kladniew, B; Castro, A; Stärkel, P; Galle, M; Crespo, R.
2020. Life Sciences, 117271
doi.org/10.1016/j.lfs.2020.117271

Induction of oxidative stress as a possible mechanism by which geraniol affects the proliferation of human A549 and HepG2 tumor cells.
Crespo, R; Rodenak-Kladniew, B. E; Castro, M. A; Soberón, M. V; Lavarías, S. M.
2020.Chemico-Biological Interactions, 109029
doi.org/10.1016/j.cbi.2020.109029

Hybrid Ofloxacin/eugenol co-loaded solid lipid nanoparticles with enhanced and targetable antimicrobial properties.
Rodenak-Kladniew, B; Montoto, S. S; Sbaraglini, M. L; Di Ianni, M; Ruiz, M. E; Talevi, A; Islan, G. A.
2019. International journal of pharmaceutics, 569, 118575
doi.org/10.1016/j.ijpharm.2019.118575

Development of biocarrier for violacein controlled release in the treatment of cancer.
Berti, I. R; Rodenak-Kladniew, B; Perez, A. A; Santiago, L; Duran, N; Castro, G. R.
2019. Reactive and Functional Polymers, 136, 122-130
doi.org/10.1016/j.reactfunctpolym.2019.01.001

Cytotoxic effects of essential oils from four Lippia alba chemotypes in human liver and lung cancer cell lines.
Montero-Villegas, S; Crespo, R; Rodenak-Kladniew, B; Castro, M. A; Galle, M; Cicció, J. F.; García De Bravo, M; Polo, M.
2018. Journal of essential oil research. ALLURED PUBL CORP, p. 1-15. ISSN 1041-2905
doi.org/10.1080/10412905.2018.1431966

Citrus reticulata peel oil inhibits nonsmall cell lung cancer cell proliferation in culture and implanted in nude mice.
Castro, M. A; Rodenak-Kladniew, B; Massone, A; Polo, M; García De Bravo, M; Crespo, R.
2018. Food & function. Royal Society of Chemistry, vol. 9, p. 2290-2299. ISSN 2042-6496
dx.doi.org/10.1039/C7FO01912B

Linalool induces cell cycle arrest and apoptosis in HepG2 cells through oxidative stress generation and modulation of Ras/MAPK and Akt/mTOR pathways.
Rodenak-Kladniew, B; Castro, A; Stärkel, P; De Saeger, C; García De Bravo, M; Crespo, R.
2018. Life sciences. PERGAMON-ELSEVIER SCIENCE LTD, vol. 199, p. 48-59. ISSN 0024-3205
doi.org/10.1016/j.lfs.2018.03.006

Simple colorimetric method to determine the in vitro antioxidant activity of different monoterpenes.
Noacco, N; Rodenak-Kladniew, B; De Bravo, M García; Castro, G. R; Islan, G. A.
2018. Analytical biochemistry. ACADEMIC PRESS INC ELSEVIER SCIENCE, vol. 555, p. 59-66. ISSN 0003-2697

Design, characterization and in vitro evaluation of linalool loaded solid lipid nanoparticles as potent tool in cancer therapy.
Rodenak-Kladniew, B; Islan, G. A; G. de Bravo, M; Durán, N; Castro, G. R.
2017. Colloids and Surfaces B: Biointerfaces 154. 123–132
doi.org/10.1016/j.colsurfb.2017.03.021

Effect of geraniol on rat cardiomyocytes and its potential use as a cardioprotective natural compound.
Crespo, R; Wei, K; Rodenak-Kladniew, B; Mercola, M; Ruiz-Lozano, P; Hurtado, C.
2017. Life Sciences, 172, 8-12 - ISSN 0024-3205

Reversible Nuclear-Lipid-Droplet Morphology Induced by Oleic Acid: A Link to Cellular-Lipid Metabolism.
Lagrutta, L. C; Montero Villegas, S; Layerenza, J. P; Sisti, M. S; García De Bravo, M.; Ves-Losada, A.
2017. Plos one. San Francisco: PUBLIC LIBRARY SCIENCE, 2017 - p. 1-25. ISSN 1932-6203

Development and tailoring of hybrid lipid nanocarriers.
Islan, G. A; Cacicedo, M. L; Rodenak Kladniew, B; Castro, G. R; Durán N.
2017. Current pharmaceutical design. Oak Park: BENTHAM SCIENCE PUBL LTD. ISSN 1381-6128

A new adenovector system for implementing thymulin gene therapy for inflammatory disorders.
Zappa-Villar, M. F; López-León, M; Pardo, J; Costa, M; Crespo, R; Dardenne, M; Goya, R. G; Reggiani, P. C.
2017. Molecular immunology: PERGAMON-ELSEVIER SCIENCE LTD. vol. 87, p. 180-187. ISSN 0161-5890

Inhibition of Mevalonate Pathway and Synthesis of the Storage Lipids in Human Liver-Derived and Non-liver Cell Lines by Lippia alba Essential Oils.
Montero-Villegas, S; Polo, M; Galle, M; Rodenak-Kladniew, B; Castro, M; Ves-Losada, A; de Bravo, M. G.
2017. Lipids, 52(1), 37-49

Modulation by geraniol of gene expression involved in lipid metabolism leading to a reduction of serum -cholesterol and triglyceride levels.
Galle, M; Rodenak Kladniew, B; Castro, M. A; Montero Villegas, S; Lacunza, E; Polo, M; García De Bravo, M; Crespo, R.
2015. Phytomedicine. Amsterdam: ELSEVIER GMBH, vol. 22, p. 696-704. ISSN 0944-7113

Suppression by geraniol of the growth of A549 human-lung adenocarcinoma cells and inhibition of the mevalonate pathway in culture and in vivo: potential use in cancer chemotherapy.
Galle, M; Crespo, R; Rodenak Kladniew, B; Montero Villegas, S; Polo, M; De Bravo, M. G.
2014. Nutrition and Cancer: LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS. vol. 66, p. 888-895. ISSN 0163-5581

Synergistic antiproliferative and anticholesterogenic effects of linalool, 1,8-cineole and simvastatin on human cell lines.
Rodenak Kladniew, B; Polo, M; Montero Villegas, S; Galle, M; Crespo, R; De Bravo, M. G.
2014. Chemico-Biological Interactions. Amsterdam: ELSEVIER IRELAND LTD,. vol. 214, p. 57-68. ISSN 0009-2797

Actividad antiproliferativa y anticolesterogénica de estatinas y monoterpenos.
Polo, M; Crespo, R; Galle, M; Rodenak Kladniew, B; Montero Villegas, S; Garcia de Bravo, M.
2013. Federación Bioquímica Provincia Buenos Aires. Acta Bioquímica Clínica Latinoamericana. vol. 47, n° 2, p. 343-351. ISSN 0325-2957

In vitro comparative analysis of antiproliferative activity of essential oil from mandarin peel and its principal component limonene.
Manassero, C; Girotti, J. R; Mijailovsky, S; García de Bravo, M; Polo, M.
2013. Natural Product Research. Londres: Taylor & Francis LTD, 2013 - vol. 27, p. 1475-1478. ISSN 1478-6419

Nuclear lipid droplets: a novel nuclear domain.
Layerenza, J. P; González, P; García de Bravo, M; Polo, M; Sisti, M. S; Ves-Losada, A.
2013. Biochimica et Biophysica Acta-Molecular and Cell Biology of Lipids. Amsterdam: ELSEVIER SCIENCE BV, 2013 -vol. 1831, p. 327-340. ISSN 1388-1981

Origen y distribución espacial de linajes maternos nativos en el noroeste y centro oeste argentinos/ Origin and spatial distribution of native maternal lineages in Northwest and Center West of Argentina.
Motti, J. M. B; Muzzio, M; Ramallo, V; Rodenak, B; Alfaro, E. L; Dipierri, J. E; Bravi, C. M; Bailliet, G.
2013. Revista argentina de Antropología Biológica. Universidad Nacional de La Plata. vol. 15, n° 1, p. 3-14. ISSN 1853-6387

Transcriptional and posttranscriptional inhibition of HMGCR and PC biosynthesis by geraniol in two HEP-G2 cellproliferation-linked pathways.
Crespo, R; Montero Villegas, S; Abba, M. C; García. De Bravo, M; Polo, M. P.
2013. Biochemistry and Cell Biology. Otawa: Natl Research Council Canada-N R C Research Press. vol. 91, p. 131-139. ISSN 0829-8211

Thymulin-based gene therapy and pituitary function in animal models of aging.
Reggiani, P. C; Poch, B; Cónsole, G. M; Rimoldi, O. J; Schwerdt, J. I; Tüngler, V; García-Bravo, M. M; Dardenne, M; Goya, R. G.
2011. Neuroimmunomodulation 18, 350-356. Editorial: Karger Medical and Scientific Publishers.

Cytotoxic and genotoxic effects of defence secretion of Ulomoides dermestoides on A549 cells.
Crespo, R; Villaverde, M. L; Girotti, J. R; Güerci, A; Juarez, M. P; García de Bravo, M.
2011. J Ethnopharmacol 136, 204–209

Geraniol and simvastatin show a synergistic effect on a human hepatocarcinoma cell line.
Polo, M. P; Crespo, R; García de Bravo, M.
2011. Cell Biochem Funct 29, 452–458

In vitro antitumor activity of N-glycosyl sulfonamides.
Crespo,R; García de Bravo, M; Colinas, P. A; Bravo, R. D.
2010. Bioorg Med Chem Lett. 20, 6469-6471

Effect of geraniol on fatty acid and mevalonate metabolism in the human hepatoma cell line Hep G2.
Polo, M. P; García de Bravo, M.
2006. Biochem Cell Biol 84,102-111. Con referato.




Quizas te interese visitar otras líneas de investigación

arrow_upward