Pt(IV)-based nanoscale coordination polymers : antitumor activity, cellular uptake and interactions with nuclear DNA
Adarsh, Nayarassery N. (Institut Català de Nanociència i Nanotecnologia)
Frias Botella, Carolina (Institut Català de Nanociència i Nanotecnologia)
Ponnoth Lohidakshan, T. M. (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Lorenzo Rivera, Julia (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Novio Vázquez, Fernando (Institut Català de Nanociència i Nanotecnologia)
Garcia-Pardo, Javier (Institut Català de Nanociència i Nanotecnologia)
Ruiz-Molina, Daniel (Institut Català de Nanociència i Nanotecnologia)

Data:	2018
Resum:	Cisplatin has been for many years the gold standard chemotherapeutic drug for the treatment of a wide range of solid tumors, even though its use is commonly associated with serious side effects including non-selective toxicity, myelosuppression or development of cisplatin resistance, among others complications. Over the last decade, a number of nanoparticle formulations were developed to reduce its side effects and improve the selectivity and efficacy of this drug. In this study, we have developed a novel nanoparticle platform based on nanoscale coordination polymer named (Zn-Pt(IV)-NCPs) which contains a Pt(IV) prodrug, Zn and the linker ligand 1,4-Bis(imidazol-1-ylmethyl)benzene (bix). The main objective has been to gain insights into the mechanism of action of this nanostructured material in comparison with cisplatin and the free Pt(IV) prodrug in order to establish a correlation between nanostructuration and therapeutic activity. Zn-Pt(IV)-NCPs nanoparticles displayed an average size close to 200 nm as determined by DLS, a good stability in physiologic environments, and a controlled drug release of Pt. In vitro studies demonstrated that Pt(IV)-NCPs showed an enhanced cytotoxic effect against cell culture of cervical cancer, neuroblastoma and human adenocarcinoma cells in comparison with free Pt(IV) prodrug. Although no difference in cell uptake of Pt was observed for any of the three cell lines assayed, a higher amount of Pt bound to the DNA was found in the cells treated with the nanostructured Pt(IV) prodrug. These studies suggest that the nanostructuration of the prodrug facilitate its activation and induce a change in the mechanism of action related to an increased interaction with the DNA as corroborated by the studies of direct interaction of the Pt(IV) prodrug, nanostructured or not, with DNA.
Ajuts:	Ministerio de Economía y Competitividad MAT2012-38318-C03-02 Ministerio de Economía y Competitividad MAT2015-70615-R Ministerio de Economía y Competitividad BIO2013-44973-R Ministerio de Economía y Competitividad BIO2016-78057-R Ministerio de Economía y Competitividad SEV-2013-0295 European Commission 629703
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Matèria:	Nanoscale coordination polymers ; Cisplatin ; Nanoparticles ; Platinum ; Platinum prodrug
Publicat a:	Chemical engineering journal, Vol. 340 (May 2018) , p. 94-102, ISSN 1873-3212

DOI: 10.1016/j.cej.2018.01.058

Postprint 29 p, 560.9 KB

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