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Inhibiting the Growth of 3D Brain Cancer Models with Bio-Coronated Liposomal Temozolomide

Nanoparticles (NPs) have emerged as an effective means to deliver anticancer drugs into the brain. Among various forms of NPs, liposomal temozolomide (TMZ) is the drug-of-choice for the treatment and management of brain tumours, but its therapeutic benefit is suboptimal. Although many possible reaso...

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Autores principales: Perini, Giordano, Giulimondi, Francesca, Palmieri, Valentina, Augello, Alberto, Digiacomo, Luca, Quagliarini, Erica, Pozzi, Daniela, Papi, Massimiliano, Caracciolo, Giulio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999290/
https://www.ncbi.nlm.nih.gov/pubmed/33809262
http://dx.doi.org/10.3390/pharmaceutics13030378
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author Perini, Giordano
Giulimondi, Francesca
Palmieri, Valentina
Augello, Alberto
Digiacomo, Luca
Quagliarini, Erica
Pozzi, Daniela
Papi, Massimiliano
Caracciolo, Giulio
author_facet Perini, Giordano
Giulimondi, Francesca
Palmieri, Valentina
Augello, Alberto
Digiacomo, Luca
Quagliarini, Erica
Pozzi, Daniela
Papi, Massimiliano
Caracciolo, Giulio
author_sort Perini, Giordano
collection PubMed
description Nanoparticles (NPs) have emerged as an effective means to deliver anticancer drugs into the brain. Among various forms of NPs, liposomal temozolomide (TMZ) is the drug-of-choice for the treatment and management of brain tumours, but its therapeutic benefit is suboptimal. Although many possible reasons may account for the compromised therapeutic efficacy, the inefficient tumour penetration of liposomal TMZ can be a vital obstacle. Recently, the protein corona, i.e., the layer of plasma proteins that surround NPs after exposure to human plasma, has emerged as an endogenous trigger that mostly controls their anticancer efficacy. Exposition of particular biomolecules from the corona referred to as protein corona fingerprints (PCFs) may facilitate interactions with specific receptors of target cells, thus, promoting efficient internalization. In this work, we have synthesized a set of four TMZ-encapsulating nanomedicines made of four cationic liposome (CL) formulations with systematic changes in lipid composition and physical−chemical properties. We have demonstrated that precoating liposomal TMZ with a protein corona made of human plasma proteins can increase drug penetration in a 3D brain cancer model derived from U87 human glioblastoma multiforme cell line leading to marked inhibition of tumour growth. On the other side, by fine-tuning corona composition we have also provided experimental evidence of a non-unique effect of the corona on the tumour growth for all the complexes investigated, thus, clarifying that certain PCFs (i.e., APO-B and APO-E) enable favoured interactions with specific receptors of brain cancer cells. Reported results open new perspectives into the development of corona-coated liposomal drugs with enhanced tumour penetration and antitumour efficacy.
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spelling pubmed-79992902021-03-28 Inhibiting the Growth of 3D Brain Cancer Models with Bio-Coronated Liposomal Temozolomide Perini, Giordano Giulimondi, Francesca Palmieri, Valentina Augello, Alberto Digiacomo, Luca Quagliarini, Erica Pozzi, Daniela Papi, Massimiliano Caracciolo, Giulio Pharmaceutics Communication Nanoparticles (NPs) have emerged as an effective means to deliver anticancer drugs into the brain. Among various forms of NPs, liposomal temozolomide (TMZ) is the drug-of-choice for the treatment and management of brain tumours, but its therapeutic benefit is suboptimal. Although many possible reasons may account for the compromised therapeutic efficacy, the inefficient tumour penetration of liposomal TMZ can be a vital obstacle. Recently, the protein corona, i.e., the layer of plasma proteins that surround NPs after exposure to human plasma, has emerged as an endogenous trigger that mostly controls their anticancer efficacy. Exposition of particular biomolecules from the corona referred to as protein corona fingerprints (PCFs) may facilitate interactions with specific receptors of target cells, thus, promoting efficient internalization. In this work, we have synthesized a set of four TMZ-encapsulating nanomedicines made of four cationic liposome (CL) formulations with systematic changes in lipid composition and physical−chemical properties. We have demonstrated that precoating liposomal TMZ with a protein corona made of human plasma proteins can increase drug penetration in a 3D brain cancer model derived from U87 human glioblastoma multiforme cell line leading to marked inhibition of tumour growth. On the other side, by fine-tuning corona composition we have also provided experimental evidence of a non-unique effect of the corona on the tumour growth for all the complexes investigated, thus, clarifying that certain PCFs (i.e., APO-B and APO-E) enable favoured interactions with specific receptors of brain cancer cells. Reported results open new perspectives into the development of corona-coated liposomal drugs with enhanced tumour penetration and antitumour efficacy. MDPI 2021-03-12 /pmc/articles/PMC7999290/ /pubmed/33809262 http://dx.doi.org/10.3390/pharmaceutics13030378 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Communication
Perini, Giordano
Giulimondi, Francesca
Palmieri, Valentina
Augello, Alberto
Digiacomo, Luca
Quagliarini, Erica
Pozzi, Daniela
Papi, Massimiliano
Caracciolo, Giulio
Inhibiting the Growth of 3D Brain Cancer Models with Bio-Coronated Liposomal Temozolomide
title Inhibiting the Growth of 3D Brain Cancer Models with Bio-Coronated Liposomal Temozolomide
title_full Inhibiting the Growth of 3D Brain Cancer Models with Bio-Coronated Liposomal Temozolomide
title_fullStr Inhibiting the Growth of 3D Brain Cancer Models with Bio-Coronated Liposomal Temozolomide
title_full_unstemmed Inhibiting the Growth of 3D Brain Cancer Models with Bio-Coronated Liposomal Temozolomide
title_short Inhibiting the Growth of 3D Brain Cancer Models with Bio-Coronated Liposomal Temozolomide
title_sort inhibiting the growth of 3d brain cancer models with bio-coronated liposomal temozolomide
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999290/
https://www.ncbi.nlm.nih.gov/pubmed/33809262
http://dx.doi.org/10.3390/pharmaceutics13030378
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