M. M. D'Elios, A. Aldinucci, R. Amoriello, M. Benagiano, E. Bonechi, P. Maggi, A. Flori, C. Ravagli, D. Saer, L. Cappiello, L. Conti, B. Valtancoli, A. Bencini, L. Menichetti, G. Baldi and C. Ballerini
Progress in nanotechnology has determined new strategies concerning drug delivery into the central
nervous system for the treatment of degenerative and inflammatory diseases. To date, brain targeting
through systemic drug administration, even in a nano-composition, is often unsuccessful. Therefore, we
investigated the possibility of loading T lymphocytes with PGLA–PEG COOH magnetite nanoparticles (30
nm), which can be built up to easily bind drugs and monoclonal antibodies, and to exploit the ability of
activated T cells to cross the blood–brain barrier and infiltrate the brain parenchyma. Iron oxide
nanoparticles have been widely used in biomedical applications due to their theranostic properties and
are therefore a well-established nanomaterial. The magnetite core is easily hybridized with polymeric
compounds that may enhance the possibility of the nanoparticles entering cells with low phagocytic
properties. Taking advantage of these material characteristics, after in vitro assessment of the viability
and functionality of nano-loaded MOG35–55 specific T cells, we transferred cells containing the nanocargo
into na¨ıve mice affected by experimental autoimmune encephalomyelitis, an animal model of
multiple sclerosis. By means of histological and immunohistological methods, we were able to identify
the nano-loaded T cells in the central nervous system. Our data demonstrated that T cells containing
nanomaterials hold the possibility of carrying and releasing nanoparticles in the brain.
Introduction
Drug delivery for the treatment of central nervous system (CNS)
diseases has been substantially improved since the advent of
nanotechnology. Indeed, the CNS is a difficult target for therapies
delivered by the systemic route due to the comprehensive
vascular organization of a physical and chemical barrier (the
blood brain barrier, BBB) and to the absence of a classical
lymphatic.1 This is the scenario faced in most neurodegenerative
diseases, including progressive phases of multiple sclerosis
(MS),
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