Mechanisms of action of antitumoral phytoactive compounds and their nanovehiculization as strategy to produce therapeutic systems
with improved properties

Team of work

Principal InvestigatorRodenak Kladniew

Rodenak Kladniew, Boris

Castro, María Agustina Castro

Research Fellow

Collaborators from other institutions

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.

Line overview

Nature is a great source of molecules with pharmacological activity. In the search of therapeutic alternatives that allow to replace or complement the current therapies, in the last years it has reemerged with great interest the study of natural compounds as a source of new drugs.
Plant-derived compounds such as flavonoids, polyphenols and terpenes have demonstrated numerous pharmacological properties, among which its among which its chemopreventive and chemotherapeutic activity stands out. Its use as phytodrugs has gained a great interest considering its natural origin, broad availability, low cost, high therapeutic potential and absence of toxic effects with relation to the available conventional drugs. Despite its great potential, its use presents limitations related to its low solubility, stability, volatility and reduced bioavailability which must be solved to improve its effectiveness.
In this context, nanotechnology appears as a powerful tool to overcome limitations related to solubility, stability, metabolism, and unspecificity of action of molecules with pharmacological activity. Nanoparticles are capable of co-encapsulating chemotherapeutic drugs and natural compounds with antitumoral activity and transporting them selectively to tumoral cells. This development arises as an improved therapeutic alternative to the current treatments.
The general objectives of the present project suggest to evaluate the antitumoral activity and the mechanisms of action of phytocompounds in 2D and 3D in-vitro models; to design, characterize and evaluate in-vitro bioactive hybrid nanoparticles containing phytocompounds that serve as low-cost therapeutic systems for the selective transport potentiated activity of antineoplastic drugs.

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

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

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

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

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.

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

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

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.

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

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

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

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

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

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

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

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

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

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.

I may be interested in visiting other lines of research