Overview of the results obtained so far in the frame of a research on suitable nanocarriers for treating myotonic dystroph

B. Stella

F. Carton

G. Lollo

I. Andreana

L. Calderan

M. Costanzo

M. Malatesta

M. Repellin

S. Arpicco

V. Guglielmi

English

Catalogo dei prodotti della ricerca

resolution and signal-to-noise ratio, holotomography representsnowadays one of the best solutions for long term live cell imagingapplications.NANOCELLULOSE AND ITS COMPOSITES IN BIOMEDI-CAL DEVICESC.A. Maestri1, N. Ferrari1, S. Meschini2, E. Pellegrini2, M. Condello2,  M. Scarpa11Department of Physics, University of Trento, Povo-Trento; and2National Center for Drug Research and Evaluation, IstitutoSuperiore di Sanità, Rome, ItalyE-mail: marina.scarpa@unitn.itNanosized cellulose (NC) is a material of natural origin obtainedby an eco-friendly procedure, in the form of fibrils (NCF) or crys-tallites (CNC). In particular, CNC prepared by carboxylation andultrasonic dispersion according to Saito et al. 1, are rod-shaped,rigid and regular nanostructures with thickness 3-5 nm and 250-500 nm length2,3. The high surface area together with the stronghydrogen bonding and cation coordination capacity, favour theinteraction of CNCs with the surrounding species.  Accordingly,CNCs are easily dispersed in water, while undergo a layer-by-layer assembly when dried and entangle in soft hydrogels by acation-driven process. CNC-derived materials show unique fea-tures in term of structure and functional properties and are suit-able for the fabrication of medical and life science devices.However, the nanotoxicity of CNC as component of biomedicaldevices is still an open question. In this presentation we willreport about the fabrication of CNC hydrogels and their incorpo-ration in nanocomposite materials. The material properties suchas microstructure, mechanical performances, and in vitro toxicityare also presented.                                                References1. Isogai A, et al. Nanoscale 2011;3:71-85. 2. Maestri CA,  et al. Mater Chem B 2017;5:8096-104. 3. Maestri CA, et al. Sci Rep 2017;7:11129.NANOCARRIERS FOR NEUROMUSCULAR DISEASESM. Costanzo1, F. Carton1,2, V. Guglielmi1, L. Calderan1, M. Repellin1,2*, G. Lollo2, I. Andreana3, S. Arpicco3, B. Stella3, M. Malatesta11Dept. of Neurosciences, Biomedicine and Movement Sciences,University of Verona, Italy; 2University of Lyon, Université ClaudeBernard Lyon 1, CNRS, LAGEPP UMR 5007, France; 3Dept. ofDrug Science & Technology, University of Turin, ItalyE-mail: manuela.malatesta@univr.itMyotonic dystrophy type 1 and 2 (DM1 and DM2) are geneticdisorders caused by CTG and CCTG expanded repeats, respec-tively. The transcribed expanded RNAs accumulate in nuclearfoci where splicing factors are sequestered, thus causing a gener-al splicing deregulation in multiple tissues. In both DMs, patho-logical traits are muscle weakness, dystrophy/atrophy andmyotonia, with disabling effects and possibly premature death.Currently, no therapy is available for DMs. Different therapeuticmolecules have been successfully tested in experimental modelsto target the expanded RNAs; however, most of the delivery ortoxicity problems remain unsolved. Our research aims at design-ing a novel therapeutic strategy using biocompatible nanoparti-cles (NPs) to administer drugs or oligonucleotides able to coun-teract RNA toxicity in DMs, with special reference to skeletalmuscle. Drug-loaded NPs may improve therapeutic efficacy byprotecting the encapsulated molecules from enzymatic degrada-tion and ensuring their delivery and sustained release inside thecell. Among the different NPs we tested, poly(lactide-co-glycol-ide) (PLGA) NPs and hyaluronic acid (HA)-based NPs proved tobe highly biocompatible for cultured murine and humanmyoblasts and myotubes1,2. We elucidated the mechanisms oftheir uptake, distribution and degradation by fluorescence andtransmission electron microscopy. We also investigated NPs dis-tribution in explanted mouse skeletal muscles maintained underfluid dynamic conditions3. Both PLGA and HA NPs proved toefficiently load pentamidine, one of the promising therapeuticagents, and preliminary results on cultured myoblasts from DM1patients demonstrated that pentamidine delivered by PLGA NPsreduced the pathological accumulation of nuclear foci with lim-ited cytotoxic effects. *INVITE project received funding from EU Horizon 2020 GANo 754345. References1. Costanzo M, et al. Nanomedicine (Lond) 2019;14(3):301-16.2. Guglielmi V, et al. Int J Pharm 2019 ;560:347-56.3. Carton F, et al. Eur J Histochem 2017;61(4):2862.HYPERTHERMIC NANOPARTICLES TO TRIGGER LIPOLYSISL. Calderan1, F. Vurro1, S. Mannucci1, F. Boschi2, S. Tambalo3, P. Lievens1,D. Prosperi4, M. Malatesta11Department of Neurosciences, Biomedicine and Movement,Anatomy and Histology Section, University of Verona; 2Department of Computer Science, Università di Verona; 3Centerfor Neuroscience and Cognitive Systems @UniTn, IstitutoItaliano di Tecnologia, Rovereto; and 4Department ofBiotechnology and Biosciences, University of Milano-Bicocca,ItalyE-mail: laura.calderan@univr.itDuring last years, evidence has been provided on the involvementof obesity in the pathogenesis and aggravation of several life-threatening diseases. In this view, we set up an innovative proto-col to induce a nanoparticle-mediated lipolysis in vitro by com-bining light and electron microscopy, and biochemical approach-es. Under appropriate administration conditions, 3T3-L1 mouseadipocytes proved to efficiently and safely internalize superpara-magnetic iron oxide nanoparticles (SPIONs), which are able toproduce heat when subjected to alternating magnetic field1-3.Thus, 3T3-L1 adipocytes were submitted to SPIONs-mediatedhyperthermia treatment (SMHT), with the aim of modulatingtheir lipid content4,5. The treatment resulted in a significant delip-idation persisting for at least 24 h, in the absence of cell death,damage or dedifferentiation. Interestingly, some factors normallylinked with lipolysis event or in lipid metabolism6 were not mod-ulated upon SMHT, suggesting the involvement of a novel/alter-native mechanism in the lipolysis observed. Notably, the sameSMHT was able to induce delipidation also in primary culturesof human adipose-derived adult stem cells. The success of thisnew approach in vitro opens promising perspectives for the appli-cation of SMHT in different biomedical fields. Next steps couldbe the use of SPIONs in an animal model of obesity, to analyzethe metabolic pathways activated by the SMHT, and the applica-tion of SMHT in an experimental model of cancer in obese miceto study the crosstalk between adipose and tumor tissues.ReferencesLee JH, et al. Nat Nanotechnol 2011;6:418-22.Guardi P, et al. ACS Nano 2012;6:3080-91.Orlando T, et al. Contrast Media Mol Imaging 2016;11:139-45.Bernabucci U, et al. J Mol Endocrinol 2009;42:139-47.Sharifi S, et al. Sci Rep 2013;3:2173.Brasaemle DL. J Lipid Res 2007;48:2547-59.7European Journal of Histochemistry 2019; vol. 63; supplement 1

Nanocarriers for neuromuscular diseases

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Nanocarriers for neuromuscular diseases

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