title: Nutlin-3 loaded nanocarriers: Preparation, characterization and in vitro antineoplastic effect against primary effusion lymphoma.
abstract: In this investigation, Nutlin-3 (Nut3), a novel antitumor drug with low water solubility (<0.1mg/L at 25°C), was loaded into liposomes (Lipo-Nut3), polymeric nanoparticles (NPs-Nut3) and nanoparticles engineered with an antibody direct against Syndecan-1/CD 138 (Syn-NPs-Nut3) to obtain carriers targeted to PEL (primary effusion lymphoma). The physicochemical properties of these carriers were determined. Atomic force microscopy showed that all the particles were well formed and spherical in shape. The presence of the antibody on surface led to a significant increase of mean diameter (280 ± 63 nm), PDI (0.3) and the shift of zeta potential towards neutrality (-1 mV). The entrapment efficiency of Lipo-Nut3, NPs-Nut3 and Syn-NPs-Nut3 was 30, 52 and 29%, and drug loading was 1.4, 4.5 and 2.6%, respectively. By performing cytofluorimetric analyses and bromodeoxyuridine (BrdU) assay, the efficacy of nanocarriers to deliver the antineoplastic drug into a PEL cell line namely BCBL-1 (immortalized body cavity B-cell lymphoma) was investigated. Two days after the treatment with 20 μM of Syn-NPs-Nut3, the cell density decreased at about 60% while the cell viability decreased at 56% only 5 days after transfection, when compared with untreated cells. A cell cycle arrest was observed with a significant decrease of cells in S-phase and increasing of apoptotic cell, if compared with untreated control. These results confirms the potential of nanocarriers approaches to deliver antitumor drug with unfavorable chemico-physical properties. Moreover, this study strongly suggests that Syn-NPs-Nut3 can be a valuable drug carrier system for the treatment of PEL lymphoma.
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Belletti
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Tosi
authors.affiliation: Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Hematology Unit, AOU Policlinico, Modena, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Riva
authors.affiliation: Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Hematology Unit, AOU Policlinico, Modena, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Lagreca
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Galliania
authors.affiliation: Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Hematology Unit, AOU Policlinico, Modena, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Luppi
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Italy.
authors.forename: M A
authors.initials: MA
authors.lastname: Vandelli
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Forni
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Italy. Electronic address: barbara.ruozi@unimore.it.
authors.forename: B
authors.initials: B
authors.lastname: Ruozi
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000737:chemistry*; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry; D054685:Lymphoma, Primary Effusion / Q000188:drug therapy*; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D010316:Particle Size; D010879:Piperazines / Q000008:administration & dosage* / Q000737:chemistry*; D016196:S Phase / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D007093:Imidazoles; D008081:Liposomes; D010879:Piperazines; C482205:nutlin 3
keywords: Anti-Syndecan-1 engineered nanoparticles; Cell cycle; Liposomes; Nutlin-3; PLGA nanoparticles; Primary effusion lymphoma