Magnetic nanoparticles (MNPs) functionalized with targeting moieties can recognize specific cell components and induce mechanical actuation under magnetic field. Their size is adequate for reaching tumors and targeting cancer cells. However, due to the nanometric size, the force generated by MNPs is smaller than the force required for largely disrupting key components of cells. Here, we show the magnetic assembly process of the nanoparticles inside the cells, to form elongated aggregates with the size required to produce elevated mechanical forces. We synthesized iron oxide nanoparticles doped with zinc, to obtain high magnetization, and functionalized with the epidermal growth factor (EGF) peptide for targeting cancer cells. Under a low frequency rotating magnetic field at 15 Hz and 40 mT, the internalized EGF-MNPs formed elongated aggregates and generated hundreds of pN to dramatically damage the plasma and lysosomal membranes. The physical disruption, including leakage of lysosomal hydrolases into the cytosol, led to programmed cell death and necrosis. Our work provides a novel strategy of designing magnetic nanomedicines for mechanical destruction of cancer cells.

SUMMARY The spinning of spider silk requires a combination of aqueous environment and stretching, and the aim of this work was to explore the role of stretching silk fibers in an aqueous environment and its effect on the tensile properties of spider silk. In particular, the sensitivity of the spider silk tensile behaviour to wet-stretching could be relevant in the search for a relationship between processing and the variability of the tensile properties. Based on this idea and working with MAS silk from Argiope trifasciata orb-web building spiders, we developed a novel procedure that permits modification of the tensile properties of spider silk: silk fibers were allowed to supercontract and subsequently stretched in water. The ratio between the length after stretching and the initial supercontracted length was used to control the process. Tensile tests performed in air, after drying, demonstrated that this simple procedure allows to predictable reproduction of the stress-strain curves of either naturally spun or forcibly silked fibers. These results suggest that the supercontracted state has a critical biological function during the spinning process of spider silk.