Electrostatic Interaction of Negatively Charged Core-Shell Nanoparticles with Antitumoral Cationic Platinum-Based Complexes

We report herein on the interaction between two cationic antiproliferative platinum compounds [namely cis-[PtCl(NH3)(2)(py)]Cl (1) and trans,trans-[(NH3)(2)Pt{NH2(CH2)(4)NH2}PtCl(NH3)(2)](Cl)(2) (2)] and novel poly(methyl methacrylate) core-shell nanoparticles (MS) bearing anionic SO3- arms, studied to determine whether such particles might serve as drug carriers for Pt drugs. Electrostatic forces hold together the resulting adducts such that in the presence of higher concentrations of other cations the Pt drug should be released quickly and easily. As expected from their electric charges, we found that the formation constant of the MS-2 adduct is significantly higher than that of MS-1. Moreover, the stability of both adducts depends on the ionic strength and surface charge density of competing cations in the medium. The stability of the conjugates and the consequent retention and release of the drug from the nanoparticles will thus depend on both blood and extracellular fluid composition.