Magnetic Nanoparticles For The Treatment Of Cancer

Abstract

The present invention relates to methods and pharmaceutical compositions for the treatment of cancer in a subject in need thereof. Therapeutic strategies using drugs which cause Lysosomal Cell Death have been proposed for eradication of resistant cancer cells. Nanotherapy based on Magnetic Intra-Lysosomal Hyperthermia (MILH) generated by magnetic nanoparticles (MNPs) that are grafted with ligands of receptors overexpressed in tumors appears to be a very promising therapeutic option. The inventors investigated the mechanisms whereby MILH induces cell death using Gastrin-grafted MNPs specifically delivered to lysosomes of tumor cells from different cancers. The inventors provide evidences that MILH causes cell death through a non-apoptotic signaling pathway. The mechanism of cell death involves temperature elevation at the nanoparticle periphery which enhances the production of reactive oxygen species through the lysosomal Fenton reaction. Subsequently, MILH induces lipid peroxidation, lysosomal membrane permeabilization and leakage of lysosomal enzymes into the cytosol, including Cathepsin-B which activates Caspase-1 but not apoptotic Caspase-3. Thus, the invention relates to a magnetic nanoparticle grafted with a tumor targeting agent for use in a method for inducing non-apoptotic signaling of cancer cell in a subject afflicted with cancer in need thereof.


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