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.

Gregori, M., Orlando, A., Re, F., Sesana, M., Nardo, L., Salerno, D., et al. (2016). Novel Antitransferrin Receptor Antibodies Improve the Blood-Brain Barrier Crossing Efficacy of Immunoliposomes. JOURNAL OF PHARMACEUTICAL SCIENCES, 105(1), 276-283 [10.1016/j.xphs.2015.11.009].

Novel Antitransferrin Receptor Antibodies Improve the Blood-Brain Barrier Crossing Efficacy of Immunoliposomes

GREGORI, MARIA
Primo
;
ORLANDO, ANTONINA
Secondo
;
RE, FRANCESCA;SESANA, MARIA SILVIA;NARDO, LUCA;SALERNO, DOMENICO;MANTEGAZZA, FRANCESCO;SALVATI, ELISA;MASSERINI, MASSIMO ERNESTO
Penultimo
;
CAZZANIGA, EMANUELA
Ultimo
2016

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.
Articolo in rivista - Articolo scientifico
blood-brain barrier; cancer; drug delivery systems; liposomes; mAb;
blood–brain barrier; cancer; drug delivery systems; liposomes; mAb
English
276
283
8
Gregori, M., Orlando, A., Re, F., Sesana, M., Nardo, L., Salerno, D., et al. (2016). Novel Antitransferrin Receptor Antibodies Improve the Blood-Brain Barrier Crossing Efficacy of Immunoliposomes. JOURNAL OF PHARMACEUTICAL SCIENCES, 105(1), 276-283 [10.1016/j.xphs.2015.11.009].
Gregori, M; Orlando, A; Re, F; Sesana, M; Nardo, L; Salerno, D; Mantegazza, F; Salvati, E; Zito, A; Malavasi, F; Masserini, M; Cazzaniga, E
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/106479
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