Tolerability to non-endosomal, micron-scale cell penetration probed with magnetic particles.

The capability of HeLa cells to internalize large spherical microparticles has been evaluated by using inorganic, magnetic microparticles of 1 and 2.8 µm of diameter. In both absence but especially under the action of a magnet, both types of particles were uptaken, in absence of cytotoxicity, by a significant percentage of cells, in a non-endosomal process clearly favored by the magnetic field. The engulfed particles efficiently drive inside the cells chemically associated proteins such as GFP and human alpha-galactosidase A, without any apparent loss of protein functionalities. While 1 µm particles are completely engulfed, at least a fraction of 2.8 µm particles remain embedded into the cell membrane, with only a fraction of their surface in cytoplasmic contact. The detected tolerance to endosomal-independent cell penetration of microscale objects is not then restricted to organic, soft materials (such as bacterial inclusion bodies) as previously described, but it is a more general phenomenon also applicable to inorganic materials. In this scenario, the use of magnetic particles in combination with external magnetic fields can represent a significant improvement in the internalization efficiency of such agents optimized as drug carriers. This fact offers a wide potential in the design and engineering of novel particulate vehicles for therapeutic, diagnostic and theragnostic applications.