Pt(IV)-based nanoscale coordination polymers: Antitumor activity, cellular uptake and interactions with nuclear DNA

N. N. Adarsh, Carolina Frias, T. M. Ponnoth Lohidakshan, Julia Lorenzo, Fernando Novio, Javier Garcia-Pardo, Daniel Ruiz-Molina

Research output: Contribution to journalArticleResearchpeer-review

18 Citations (Scopus)

Abstract

© 2018 Elsevier B.V. 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.
Original languageEnglish
Pages (from-to)94-102
JournalChemical Engineering Journal
Volume340
DOIs
Publication statusPublished - 15 May 2018

Keywords

  • Cisplatin
  • Nanoparticles
  • Nanoscale coordination polymers
  • Platinum
  • Platinum prodrug

Fingerprint Dive into the research topics of 'Pt(IV)-based nanoscale coordination polymers: Antitumor activity, cellular uptake and interactions with nuclear DNA'. Together they form a unique fingerprint.

Cite this