Polymer nanoparticles of N-vinylpyrrolidone loaded with an organic aminonitroxyl platinum (iv) complex. Characterization and investigation of their in vitro cytotoxicity

Abstract

The conditions for obtaining stable aqueous solutions of a lipophilic aminonitroxyl platinum complex, namely, e-amine-d-(4-amino-2,2,6,6-tetramethylpiperidine 1-oxyl)-a, f-bis(octanoato)-b, c-dichloroplatinum(iv), by means of its encapsulation into nanoparticles of copolymers of N-vinylpyrrolidone with triethylene glycol dimethacrylate with various monomer compositions and topologies were found. Aqueous solutions of the complex encapsulated into polymer particles were investigated by dynamic light scattering, the temperature dependence of nanostructure sizes was studied. Transmission electron microscopy established that the hybrid nanostructures are core—shell particles, in which the platinum complex forms small clusters (∼4 nm). The parameters of ESR spectra of aqueous dispersions indicate a high mobility of nitroxyl contained in hybrid nanostructures. Voltammetric measurements demonstrate a similarity of the redox reactions related to the free radical fragment of the aminonitroxyl PtIV complex and of the 4-acetylamino-2,2,6,6-tetramethylpiperidine 1-oxyl radical. Polymer products containing the platinum complex were studied by IR spectroscopy, TGA, and DSC. The cytotoxicity index (IC50) of the free and the encapsulated complex was determined for HeLa tumor cells. The cytotoxicity of the latter (IC50 47–205 nmol L−1) depends on the monomeric composition of the nanoparticles and the incubation time.