4.7 Article

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

期刊

出版社

ELSEVIER
DOI: 10.1016/j.colsurfb.2021.112123

关键词

Magnetic particles; Cell penetration; Cellular therapy; Recombinant protein; Human alpha-galactosidase A

资金

  1. Instituto de Salud Carlos III, through Acciones CIBER''
  2. VI National R&D&I Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions
  3. Instituto de Salud Carlos III
  4. AGAUR [2017SGR-229]
  5. ICREA ACADEMIA award
  6. European Regional Development Fund

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HeLa cells are able to internalize large spherical microparticles, especially when under the influence of a magnetic field. The particles, once engulfed, effectively transport chemically associated proteins into the cells, with the efficiency of internalization depending on the diameter of the particles.
The capability of HeLa cells to internalize large spherical microparticles has been evaluated by using inorganic, magnetic microparticles of 1 and 2.8 mu m 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 nonendosomal 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 mu m particles are completely engulfed, at least a fraction of 2.8 mu m 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.

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