title: Nanoparticle-based strategy for personalized B-cell lymphoma therapy.
abstract: B-cell lymphoma is associated with incomplete response to treatment, and the development of effective strategies targeting this disease remains challenging. A new personalized B-cell lymphoma therapy, based on a site-specific receptor-mediated drug delivery system, was developed in this study. Specifically, natural silica-based nanoparticles (diatomite) were modified to actively target the antiapoptotic factor B-cell lymphoma/leukemia 2 (Bcl2) with small interfering RNA (siRNA). An idiotype-specific peptide (Id-peptide) specifically recognized by the hypervariable region of surface immunoglobulin B-cell receptor was exploited as a homing device to ensure specific targeting of lymphoma cells. Specific nanoparticle uptake, driven by the Id-peptide, was evaluated by flow cytometry and confocal microscopy and was increased by approximately threefold in target cells compared with nonspecific myeloma cells and when a random control peptide was used instead of Id-peptide. The specific internalization efficiency was increased by fourfold when siRNA was also added to the modified nanoparticles. The modified diatomite particles were not cytotoxic and their effectiveness in downregulation of gene expression was explored using siRNA targeting Bcl2 and evaluated by quantitative real-time polymerase chain reaction and Western blot analyses. The resulting gene silencing observed is of significant biological importance and opens new possibilities for the personalized treatment of lymphomas.
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University Federico II of Naples, Naples.
authors.forename: Nicola M
authors.initials: NM
authors.lastname: Martucci
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University Federico II of Naples, Naples.
authors.forename: Nunzia
authors.initials: N
authors.lastname: Migliaccio
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University Federico II of Naples, Naples.
authors.forename: Immacolata
authors.initials: I
authors.lastname: Ruggiero
authors.affiliation: Department of Experimental and Clinical Medicine, University of Catanzaro "Magna Graecia", Catanzaro.
authors.forename: Francesco
authors.initials: F
authors.lastname: Albano
authors.affiliation: Institute of Endocrinology and Molecular Oncology.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Calì
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University Federico II of Naples, Naples.
authors.forename: Simona
authors.initials: S
authors.lastname: Romano
authors.affiliation: Institute for Microelectronics and Microsystems, National Research Council, Naples, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Terracciano
authors.affiliation: Institute for Microelectronics and Microsystems, National Research Council, Naples, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Rea
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University Federico II of Naples, Naples.
authors.forename: Paolo
authors.initials: P
authors.lastname: Arcari
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University Federico II of Naples, Naples.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Lamberti
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D020868:Gene Silencing; D019254:Genes, bcl-2 / Q000235:genetics*; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000235:genetics; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D058990:Molecular Targeted Therapy; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D057285:Precision Medicine / Q000379:methods; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000951:Antigens, Neoplasm; C464525:Id tumor-specific protein, mouse; D034741:RNA, Small Interfering
keywords: Bcl2; active targeting; diatomite; personalized therapy; small interfering RNA