TY - JOUR
T1 - H-Ferritin nanoparticle-mediated delivery of antibodies across a BBB in vitro model for treatment of brain malignancies
AU - Rizzuto, Maria Antonietta
AU - Dal Magro, Roberta
AU - Barbieri, Linda
AU - Pandolfi, Laura
AU - Sguazzini-Viscontini, Anna
AU - Truffi, Marta
AU - Salvioni, Lucia
AU - Corsi, Fabio
AU - Colombo, Miriam
AU - Re, Francesca
AU - Prosperi, Davide
N1 - Funding Information:
The research leading to these results has received funding from AIRC under IG 2018 – ID. 21565 project – P.I. Prosperi Davide. Support to this work was also provided by Regione Lombardia POR FESR 2014-2020 (Call HUB Ricerca ed Innovazione: ImmunHUB) and by MIUR (PRIN 2017, ID 2017E3A2NR project).
Publisher Copyright:
© 2021 The Royal Society of Chemistry.
PY - 2021/3/21
Y1 - 2021/3/21
N2 - Brain cancers are a group of neoplasms that can be either primary, such as glioblastoma multiforme (GBM), or metastatic, such as the HER2+ breast cancer brain metastasis. The brain represents a sanctuary for cancer cells thanks to the presence of the blood brain barrier (BBB) that controls trafficking of molecules, protecting the brain from toxic substances including drugs. Considering that GBM and HER2+ breast cancer brain metastases are characterized by EGFR and HER2 over-expression respectively, CTX- and TZ-based treatment could be effective. Several studies show that these monoclonal antibodies (mAbs) exert both a cytostatic activity interfering with the transduction pathways of EGFR family and a cytotoxic activity mainly through the immune system activation via the antibody dependent cell-mediated cytotoxicity (ADCC). Since the major limitation to therapeutic mAbs application is the presence of the BBB, here we use a recombinant form of human apoferritin (HFn) as a nanovector to promote the delivery of mAbs to the brain for the activation of the ADCC response. Using a transwell model of the BBB we proved the crossing ability of HFn-mAb. Cellular uptake of HFn-mAb by human cerebral microvascular endothelial cells (hCMEC/D3) was demonstrated by confocal microscopy. Moreover, after crossing the endothelial monolayer, HFn-conjugated mAbs retain their biological activity against targets, as assessed by MTS and ADCC assays. Our data support the use of HFn as efficient carrier to enhance the BBB crossing of mAbs, without affecting their antitumoral activity.
AB - Brain cancers are a group of neoplasms that can be either primary, such as glioblastoma multiforme (GBM), or metastatic, such as the HER2+ breast cancer brain metastasis. The brain represents a sanctuary for cancer cells thanks to the presence of the blood brain barrier (BBB) that controls trafficking of molecules, protecting the brain from toxic substances including drugs. Considering that GBM and HER2+ breast cancer brain metastases are characterized by EGFR and HER2 over-expression respectively, CTX- and TZ-based treatment could be effective. Several studies show that these monoclonal antibodies (mAbs) exert both a cytostatic activity interfering with the transduction pathways of EGFR family and a cytotoxic activity mainly through the immune system activation via the antibody dependent cell-mediated cytotoxicity (ADCC). Since the major limitation to therapeutic mAbs application is the presence of the BBB, here we use a recombinant form of human apoferritin (HFn) as a nanovector to promote the delivery of mAbs to the brain for the activation of the ADCC response. Using a transwell model of the BBB we proved the crossing ability of HFn-mAb. Cellular uptake of HFn-mAb by human cerebral microvascular endothelial cells (hCMEC/D3) was demonstrated by confocal microscopy. Moreover, after crossing the endothelial monolayer, HFn-conjugated mAbs retain their biological activity against targets, as assessed by MTS and ADCC assays. Our data support the use of HFn as efficient carrier to enhance the BBB crossing of mAbs, without affecting their antitumoral activity.
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U2 - 10.1039/d0bm01726d
DO - 10.1039/d0bm01726d
M3 - Article
C2 - 33544109
AN - SCOPUS:85103102111
VL - 9
SP - 2032
EP - 2042
JO - Biomaterials Science
JF - Biomaterials Science
SN - 2047-4830
IS - 6
ER -