title: Novel Antitransferrin Receptor Antibodies Improve the Blood-Brain Barrier Crossing Efficacy of Immunoliposomes.
abstract: Surface functionalization with antitransferrin receptor (TfR) mAbs has been suggested as the strategy to enhance the transfer of nanoparticles (NPs) across the blood-brain barrier (BBB) and to carry nonpermeant drugs from the blood into the brain. However, the efficiency of BBB crossing is currently too poor to be used in vivo. In the present investigation, we compared 6 different murine mAbs specific for different epitopes of the human TfR to identify the best performing one for the functionalization of NPs. For this purpose, we compared the ability of mAbs to cross an in vitro BBB model made of human brain capillary endothelial cells (hCMEC/D3). Liposomes functionalized with the best performing mAb (MYBE/4C1) were uptaken, crossed the BBB in vitro, and facilitated the BBB in vitro passage of doxorubicin, an anticancer drug, 3.9 folds more than liposomes functionalized with a nonspecific IgG, as assessed by confocal microscopy, radiochemical techniques, and fluorescence, and did not modify the cell monolayer structural or functional properties. These results show that MYBE/4C1 antihuman TfR mAb is a powerful resource for the enhancement of BBB crossing of NPs and is therefore potentially useful in the treatment of neurologic diseases and disorders including brain carcinomas.
authors: Department of Health Sciences and Nanomedicine Center NANOMIB, University of Milano-Bicocca, 20900 Monza, Italy. Electronic address: maria.gregori1@unimib.it.
authors: Maria
authors: M
authors: Gregori
authors: Department of Health Sciences and Nanomedicine Center NANOMIB, University of Milano-Bicocca, 20900 Monza, Italy.
authors: Antonina
authors: A
authors: Orlando
authors: Department of Health Sciences and Nanomedicine Center NANOMIB, University of Milano-Bicocca, 20900 Monza, Italy.
authors: Francesca
authors: F
authors: Re
authors: Department of Health Sciences and Nanomedicine Center NANOMIB, University of Milano-Bicocca, 20900 Monza, Italy.
authors: Silvia
authors: S
authors: Sesana
authors: Department of Health Sciences and Nanomedicine Center NANOMIB, University of Milano-Bicocca, 20900 Monza, Italy.
authors: Luca
authors: L
authors: Nardo
authors: Department of Health Sciences and Nanomedicine Center NANOMIB, University of Milano-Bicocca, 20900 Monza, Italy.
authors: Domenico
authors: D
authors: Salerno
authors: Department of Health Sciences and Nanomedicine Center NANOMIB, University of Milano-Bicocca, 20900 Monza, Italy.
authors: Francesco
authors: F
authors: Mantegazza
authors: IFOM, the FIRC Institute for Molecular Oncology Foundation, IFOM-IEO Campus, 20139 Milano, Italy.
authors: Elisa
authors: E
authors: Salvati
authors: Department of Medical Sciences, Laboratory of Immunogenetics and CeRMS, University of Torino, Torino, Italy.
authors: Andrea
authors: A
authors: Zito
authors: Department of Medical Sciences, Laboratory of Immunogenetics and CeRMS, University of Torino, Torino, Italy; Transplant Immunology, Città della Salute e della Scienza, Torino, Italy.
authors: Fabio
authors: F
authors: Malavasi
authors: Department of Health Sciences and Nanomedicine Center NANOMIB, University of Milano-Bicocca, 20900 Monza, Italy.
authors: Massimo
authors: M
authors: Masserini
authors: Department of Health Sciences and Nanomedicine Center NANOMIB, University of Milano-Bicocca, 20900 Monza, Italy.
authors: Emanuela
authors: E
authors: Cazzaniga
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics; D019138:Antibodies, Blocking / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002196:Capillaries / Q000187:drug effects / Q000378:metabolism; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D042783:Endothelial Cells; D000939:Epitopes; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D008081:Liposomes; D051379:Mice; D010316:Particle Size; D011990:Receptors, Transferrin / Q000037:antagonists & inhibitors*
chemical_list: D000903:Antibiotics, Antineoplastic; D019138:Antibodies, Blocking; D000939:Epitopes; D007074:Immunoglobulin G; D008081:Liposomes; D011990:Receptors, Transferrin; D004317:Doxorubicin
keywords: blood–brain barrier; cancer; drug delivery systems; liposomes; mAb