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Multimodal imaging for a theranostic approach in a murine model of B-cell lymphoma with engineered nanoparticles
Authors:Enza Torino  Luigi Auletta  Donatella Vecchione  Francesca Maria Orlandella  Giuliana Salvatore  Enrico Iaccino  Dario Fiorenza  Anna Maria Grimaldi  Annamaria Sandomenico  Sandra Albanese  Daniela Sarnataro  Matteo Gramanzini  Camillo Palmieri  Giuseppe Scala  Ileana Quinto  Paolo Antonio Netti  Marco Salvatore  Adelaide Greco
Affiliation:1. Istituto Italiano di Tecnologia, IIT - Center for Advanced Biomaterials for Health Care, CABHC@CRIB, Napoli, Italia;2. Centro Interdipartimentale di Ricerca sui Biomateriali, Università degli Studi di Napoli Federico II, Napoli, Italia;3. Dipartimento di Ingegneria Chimica, dei Materiali e della Produzione Industriale, Università degli Studi di Napoli Federico II, Napoli, Italia;4. IRCCS SDN S.p.A., Napoli, Italia;5. Dipartimento di Scienze Motorie e del Benessere, Università “Parthenope”, Napoli, Italia;6. Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi “Magna Graecia" di Catanzaro, Catanzaro, Italia;g. IBB, CNR, Napoli, Italia;h. CEINGE Biotecnologie Avanzate, s.c.ar.l., Napoli, Italia;i. Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Napoli, Italia;j. Dipartimento di Scienze Biomediche Avanzate, Università degli Studi di Napoli Federico II, Napoli, Italia
Abstract:Nanoparticles (NPs) are a promising tool for in vivo multimodality imaging and theranostic applications. Hyaluronic acid (HA)-based NPs have numerous active groups that make them ideal as tumor-targeted carriers. The B-lymphoma neoplastic cells express on their surfaces a clone-specific immunoglobulin receptor (Ig-BCR). The peptide A20-36 (pA20-36) selectively binds to the Ig-BCR of A20 lymphoma cells. In this work, we demonstrated the ability of core-shell chitosan-HA-NPs decorated with pA20-36 to specifically target A20 cells and reduce the tumor burden in a murine xenograft model. We monitored tumor growth using high-frequency ultrasonography and demonstrated targeting specificity and kinetics of the NPs via in vivo fluorescent reflectance imaging. This result was also confirmed by ex vivo magnetic resonance imaging and confocal microscopy. In conclusion, we demonstrated the ability of NPs loaded with fluorescent and paramagnetic tracers to act as multimodal imaging contrast agents and hence as a non-toxic, highly specific theranostic system.
Keywords:Mouse model  Preclinical imaging  Theranostic  Fluorescence imaging  Magnetic resonance  Engineered nanoparticles  HA  Hyaluronic acid  NPs  nanoparticles  Ig-BCR  immunoglobulin B-cell receptor  pA20-36  peptide A20-36  pCNT  scrambled or control peptide  MRI  magnetic resonance imaging  FRI  fluorescent reflectance imaging  Ch  chitosan  Mw  molecular weight  TPP  sodium tripolyphosphate  EtOH  ethanol  Gd-DTPA  gadolinium diethylene-triamine-pent-acetate  EDC  1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride  NHS  N-hydroxysuccinimide  pCNT  scrambled control peptide  DVS  divinyl sulfone  PEG  polyethylene glycol  FITC  fluorescein isothiocyanate  Ex/Em  excitation/emission  Cy7  cyanine7  STED  stimulated emission depletion  PBS  phosphate-buffered saline  BCA  Bicinchoninic Acid Protein  OD  optical density  SEM  scanning electron microscope  TEM  transmission electron microscope  DLS  dynamic light scattering  CPC  Carr-Purcell sequence  RPMI  Roswell Park Memorial Institute  HFUS  high frequency ultrasound  SE  standard error of the mean  RM-ANOVA  repeated measures analysis of variance  FlS  fluorescence reflectance signal  DAPI  4′,6-diamino-2-phenylindole?2HCl
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