title: Lipid-based nanoparticles containing cationic derivatives of PTA (1,3,5-triaza-7-phosphaadamantane) as innovative vehicle for Pt complexes: Production, characterization and in vitro studies.
abstract: The aliphatic phosphine PTA (1,3,5-triaza-7-phosphaadamantane) is a promising ligand for metal complexes designed and developed as innovative inorganic drugs. In the present paper, an N-alkylated derivative of PTA, (PTAC16H33)X (X=I, C1, or X=PF6, C2) and its platinum coordination complex cis-[PtCl2(PTAC16H33)2](PF6)2, C3, were considered as components of cationic lipid nanoparticles (CLNs). Particularly, CLN1, CLN2 and CLN3 were obtained by adding derivatives C1, C2 or C3 during nanoparticles preparation, while CLN2-Pt were obtained by treating preformed CLN2 with Pt(II). It was demonstrated that CLN1, CLN2 and CLN3 can be produced with technological conventional methods. However, among the two here proposed protocols, the one based on the treatment of preformed nanoparticles appears more advantageous as compared to the other since it allows a quantitative association yield of Pt. As determined by ICP-OES, a content of P and Pt 2.2-fold and 2.5-fold higher in CLN2-Pt than in CLN3 was evidenced. For the first time was demonstrated that properly functionalized preformed nanoparticles can be efficiently used to obtain a post production Pt(II) complex while maintaining a cytotoxic activity toward cultured cells. In fact, the antiproliferative activity shown by CLN3, CLN2-Pt on the three model cancer cell lines was substantially similar and comparable to that of complex C3 in dmso solution. Thus N-alkylated-PTA derivatives in CLNs could be proposed as innovative biocompatible and water dispersible nanoparticles carrying lipophilic Pt complexes becoming an interesting and improved system with respect to dmso solution.
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy; Nanopharmanet: The Italian Network of Pharmaceutical Nanotechnology and Nanomedicine, Italy. Electronic address: crt@unife.it.
authors.forename: Rita
authors.initials: R
authors.lastname: Cortesi
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Damiani
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Ravani
authors.affiliation: Department of Chemistry and Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Marvelli
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Esposito
authors.affiliation: Macromolecular Chemistry II, University of Bayreuth, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Drechsler
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ferrara, Ferrara, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Pagnoni
authors.affiliation: Department of Life and Environmental Sciences and CNISM, Polytechnic University of Marche, Ancona, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Mariani
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Sforza
authors.affiliation: Nanopharmanet: The Italian Network of Pharmaceutical Nanotechnology and Nanomedicine, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Bergamini
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000737:chemistry* / Q000494:pharmacology; D010984:Platinum / Q000737:chemistry* / Q000494:pharmacology
chemical_list: C501763:1,3,5-triaza-7-phosphaadamantane; D000970:Antineoplastic Agents; D056831:Coordination Complexes; D008055:Lipids; D009943:Organophosphorus Compounds; D010984:Platinum; D004247:DNA; D000218:Adamantane
keywords: Antiproliferative activity; Cationic lipid nanoparticles; Cisplatin; PTA; Pt complexes