Temozolomide (TMZ) is the current first-line chemotherapy for treatment of glioblastoma multiforme (GBM). However, similar to other brain therapeutic compounds, access of TMZ to brain tumors is impaired by the blood-brain barrier (BBB) leading to poor response for GBM patients. To overcome this major hurdle, we have synthesized a set of TMZ-encapsulating nanomedicines made of four cationic liposome (CL) formulations with systematic changes in lipid composition and physical-chemical properties. The targeting nature of this nanomedicine is provided by the recruitment of proteins, with natural targeting capacity, in the biomolecular corona (BC) layer that forms around CLs after exposure to human plasma (HP). TMZ-loaded CL-BC complexes were thoroughly characterized by dynamic light scattering (DLS), electrophoretic light scattering (ELS), and nanoliquid chromatography tandem mass spectrometry (nano-LC MS/MS). BCs were found to be enriched of typical BC fingerprints (BCFs) (e.g., Apolipoproteins, Vitronectin, and vitamin K-dependent protein), which have a substantial capacity in binding to receptors that are overexpressed at the BBB (e.g., scavenger receptor class B, type I and low-density lipoprotein receptor). We found that the CL formulation exhibiting the highest levels of targeting BCFs had larger uptake in human umbilical vein endothelial cells (HUVECs) that are commonly used as an in vitro model of the BBB. This formulation could also deliver TMZ to the human glioblastoma U-87 MG cell line and thus substantially enhance their antitumor efficacy compared to corona free CLs. Thus, we propose that the BC-based nanomedicines may pave a more effective way for efficient treatment of GBM.

Brain Targeting by Liposome-Biomolecular Corona Boosts Anticancer Efficacy of Temozolomide in Glioblastoma Cells / Arcella, Antonietta; Palchetti, Sara; Digiacomo, Luca; Pozzi, Daniela; Capriotti, Anna Laura; Frati, Luigi; Oliva, Maria Antonietta; Tsaouli, Georgia; Rota, Rossella; Screpanti, Isabella; Mahmoudi, Morteza; Caracciolo, Giulio. - In: ACS CHEMICAL NEUROSCIENCE. - ISSN 1948-7193. - 9:12(2018), pp. 3166-3174. [10.1021/acschemneuro.8b00339]

Brain Targeting by Liposome-Biomolecular Corona Boosts Anticancer Efficacy of Temozolomide in Glioblastoma Cells

Arcella, Antonietta;Palchetti, Sara;Digiacomo, Luca;Pozzi, Daniela;Capriotti, Anna Laura;Frati, Luigi;Oliva, Maria Antonietta;Tsaouli, Georgia;Screpanti, Isabella;Caracciolo, Giulio
2018

Abstract

Temozolomide (TMZ) is the current first-line chemotherapy for treatment of glioblastoma multiforme (GBM). However, similar to other brain therapeutic compounds, access of TMZ to brain tumors is impaired by the blood-brain barrier (BBB) leading to poor response for GBM patients. To overcome this major hurdle, we have synthesized a set of TMZ-encapsulating nanomedicines made of four cationic liposome (CL) formulations with systematic changes in lipid composition and physical-chemical properties. The targeting nature of this nanomedicine is provided by the recruitment of proteins, with natural targeting capacity, in the biomolecular corona (BC) layer that forms around CLs after exposure to human plasma (HP). TMZ-loaded CL-BC complexes were thoroughly characterized by dynamic light scattering (DLS), electrophoretic light scattering (ELS), and nanoliquid chromatography tandem mass spectrometry (nano-LC MS/MS). BCs were found to be enriched of typical BC fingerprints (BCFs) (e.g., Apolipoproteins, Vitronectin, and vitamin K-dependent protein), which have a substantial capacity in binding to receptors that are overexpressed at the BBB (e.g., scavenger receptor class B, type I and low-density lipoprotein receptor). We found that the CL formulation exhibiting the highest levels of targeting BCFs had larger uptake in human umbilical vein endothelial cells (HUVECs) that are commonly used as an in vitro model of the BBB. This formulation could also deliver TMZ to the human glioblastoma U-87 MG cell line and thus substantially enhance their antitumor efficacy compared to corona free CLs. Thus, we propose that the BC-based nanomedicines may pave a more effective way for efficient treatment of GBM.
biomolecular corona; drug delivery; glioblastoma; nanobio interface; nanomedicine; temozolomide; biochemistry; physiology; cognitive neuroscience; cell biology
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Brain Targeting by Liposome-Biomolecular Corona Boosts Anticancer Efficacy of Temozolomide in Glioblastoma Cells / Arcella, Antonietta; Palchetti, Sara; Digiacomo, Luca; Pozzi, Daniela; Capriotti, Anna Laura; Frati, Luigi; Oliva, Maria Antonietta; Tsaouli, Georgia; Rota, Rossella; Screpanti, Isabella; Mahmoudi, Morteza; Caracciolo, Giulio. - In: ACS CHEMICAL NEUROSCIENCE. - ISSN 1948-7193. - 9:12(2018), pp. 3166-3174. [10.1021/acschemneuro.8b00339]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1247472
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