In this study, a general approach for the multifunctionalization of magnetic nanoparticles (MNPs) with drugs (Doxorubicin and Gemcitabine) and targeting moieties (Nucant pseudopeptide) for controlled and selective release is described. The functionalization is achieved by the formation of disulfide bonds between MNPs and drugs derivatives synthesized in this work. Our strategy consists in the introduction of a pyridyldisulfide moiety to the drugs that react efficiently with sulfhydryl groups of pre-activated MNPs. This approach also allows the quantification of the covalently immobilized drug by measuring the amount of the 2-pyridinethione released during the process. The linkers developed here allow the release of drugs without any chemical modification. This process is triggered under highly reducing environment, such as that present inside the cells. Complete release of drugs is achieved within 5-8 h under intracellular conditions whereas negligible percentage of release is observed in extracellular conditions. We propose here a modular general approach for the functionalization of nanoparticles that can be used for different types of drugs and targeting agents.
Keywords: Anticancer therapy; Controlled drug release; Disulfide bond; Magnetic nanoparticles; Multifunctionalization; Nanomedicine.
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