title: Cell uptake and intracellular fate of phospholipidic manganese-based nanoparticles.
abstract: During the last decades, several studies have proposed manganese (Mn) complexes as alternative contrast agents for magnetic resonance imaging (MRI). With the nanotechnology surge in recent years, different types of Mn-based nanoparticles (Nps) have been developed. However, to design effective and safe administration procedures, preliminary studies on target cells, aimed at verifying their full biocompatibility and biodegradability, are mandatory. In this study, MnO containing-Nps encapsulated in a phospholipidic shell (PL-MnO Nps) were tested in cultured cells and flow cytometry; confocal and transmission electron microscopy were combined to understand the Nps uptake mechanism, intracellular distribution and degradation pathways, as well as possible organelle alterations. The results demonstrated that PL-MnO Nps undergo rapid and massive cell internalization, and persist free in the cytoplasm before undergoing lysosomal degradation without being cytotoxic or inducing subcellular damage. Based on the results with this cell model in vitro, PL-MnO Nps thus proved to be suitably biocompatible, and may be envisaged as very promising tools for therapeutic and diagnostic applications, as drug carriers or contrast agent for MRI.
authors.affiliation: Dipartimento di Neuroscienze, Biomedicina e Movimento, Sezione di Anatomia e Istologia, Università di Verona, Strada Le Grazie 8, 37134 Verona, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Costanzo
authors.affiliation: Dipartimento di Scienza e Tecnologia del Farmaco, Università di Torino, Via P. Giuria 9, 10125 Torino, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Scolaro
authors.affiliation: Dipartmento di Chimica and NIS (Nanostructured Interfaces and Surfaces) Centre, Università di Torino, Via P. Giuria 7, 10125 Torino, Italy.
authors.forename: Gloria
authors.initials: G
authors.lastname: Berlier
authors.affiliation: Dipartimento di Scienza e Tecnologia del Farmaco, Università di Torino, Via P. Giuria 9, 10125 Torino, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Marengo
authors.affiliation: Dipartimento di Neuroscienze, Biomedicina e Movimento, Sezione di Anatomia e Istologia, Università di Verona, Strada Le Grazie 8, 37134 Verona, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Grecchi
authors.affiliation: Dipartimento di Neuroscienze, Biomedicina e Movimento, Sezione di Anatomia e Istologia, Università di Verona, Strada Le Grazie 8, 37134 Verona, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Zancanaro
authors.affiliation: Dipartimento di Neuroscienze, Biomedicina e Movimento, Sezione di Anatomia e Istologia, Università di Verona, Strada Le Grazie 8, 37134 Verona, Italy. Electronic address: manuela.malatesta@univr.it.
authors.forename: Manuela
authors.initials: M
authors.lastname: Malatesta
authors.affiliation: Dipartimento di Scienza e Tecnologia del Farmaco, Università di Torino, Via P. Giuria 9, 10125 Torino, Italy. Electronic address: silvia.arpicco@unito.it.
authors.forename: Silvia
authors.initials: S
authors.lastname: Arpicco
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism*; D017895:Manganese Compounds / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D010087:Oxides / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology; D010743:Phospholipids / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D003287:Contrast Media; D017895:Manganese Compounds; D010087:Oxides; D010743:Phospholipids; C027424:manganese oxide
keywords: Cell uptake; Fluorescence microscopy; Manganese; Nanoparticles; Transmission electron microscopy