Mithramycin delivery systems to develop effective therapies in sarcomas
| Autor: | Pilar Clemente-Casares, Francisco Morís, Aitana Vallina-Álvarez, Aida Rodríguez, Verónica Blanco-Lorenzo, Juan Tornin, Oscar Estupiñan, Iván Bravo, Borja Gallego, Carlos Alonso-Moreno, Enrique Niza, M. Victoria Gonzalez, Mar Rodríguez-Santamaría, Daniel Hermida-Merino, Alberto Ocaña, Veronica Rey, Rene Rodriguez |
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| Přispěvatelé: | Universitat Politècnica de Catalunya. Departament de Ciència i Enginyeria de Materials, Universitat Politècnica de Catalunya. BBT - Biomaterials, Biomecànica i Enginyeria de Teixits, Instituto de Investigación Sanitaria del Principado de Asturias |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Oncologia
Drug Compounding Polyesters Biomedical Engineering Chondrosarcoma Pharmaceutical Science Medicine (miscellaneous) Mice Nude Bioengineering Antineoplastic Agents Pharmacology Polylactide Applied Microbiology and Biotechnology Undifferentiated Pleomorphic Sarcoma Medicaments antineoplàstics Polymeric nanoparticles Mice Therapeutic index Mithramycin Antineoplastic agents medicine Medical technology Animals Humans R855-855.5 Liposome Soft tissue sarcoma Chemistry Cancer stem cells Research Enginyeria biomèdica [Àrees temàtiques de la UPC] In vitro toxicology Sarcoma Hydrogels Plicamycin medicine.disease Anti-Bacterial Agents Self-healing hydrogels Liposomes Molecular Medicine Nanoparticles Female Nanocarriers TP248.13-248.65 Small unilamellar vesicles liposomes Biotechnology |
| Zdroj: | Journal of Nanobiotechnology Journal of Nanobiotechnology, Vol 19, Iss 1, Pp 1-21 (2021) UPCommons. Portal del coneixement obert de la UPC Universitat Politècnica de Catalunya (UPC) |
| ISSN: | 1477-3155 |
| Popis: | Background Sarcomas comprise a group of aggressive malignancies with very little treatment options beyond standard chemotherapy. Reposition of approved drugs represents an attractive approach to identify effective therapeutic compounds. One example is mithramycin (MTM), a natural antibiotic which has demonstrated a strong antitumour activity in several tumour types, including sarcomas. However, its widespread use in the clinic was limited by its poor toxicity profile. Results In order to improve the therapeutic index of MTM, we have loaded MTM into newly developed nanocarrier formulations. First, polylactide (PLA) polymeric nanoparticles (NPs) were generated by nanoprecipitation. Also, liposomes (LIP) were prepared by ethanol injection and evaporation solvent method. Finally, MTM-loaded hydrogels (HG) were obtained by passive loading using a urea derivative non-peptidic hydrogelator. MTM-loaded NPs and LIP display optimal hydrodynamic radii between 80 and 105 nm with a very low polydispersity index (PdI) and encapsulation efficiencies (EE) of 92 and 30%, respectively. All formulations show a high stability and different release rates ranging from a fast release in HG (100% after 30 min) to more sustained release from NPs (100% after 24 h) and LIP (40% after 48 h). In vitro assays confirmed that all assayed MTM formulations retain the cytotoxic, anti-invasive and anti-stemness potential of free MTM in models of myxoid liposarcoma, undifferentiated pleomorphic sarcoma and chondrosarcoma. In addition, whole genome transcriptomic analysis evidenced the ability of MTM, both free and encapsulated, to act as a multi-repressor of several tumour-promoting pathways at once. Importantly, the treatment of mice bearing sarcoma xenografts showed that encapsulated MTM exhibited enhanced therapeutic effects and was better tolerated than free MTM. Conclusions Overall, these novel formulations may represent an efficient and safer MTM-delivering alternative for sarcoma treatment. Graphical abstract |
| Databáze: | OpenAIRE |
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