Collaborative membrane activity and receptor-dependent tumor cell targeting for precise nanoparticle delivery in CXCR4(+) colorectal cancer
Por:
Sala R, Sánchez-García L, Serna N, Céspedes MV, Casanova I, Roldan-Molina M, Sánchez-Chardi A, Unzueta U, Vázquez E, Mangues R and Villaverde A
Publicada:
1 nov 2019
Ahead of Print:
5 sep 2019
Resumen:
By the appropriate selection of functional peptides and proper accommodation sites, we have generated a set of multifunctional proteins that combine selectivity for CXCR4(+) cell binding and relevant endosomal escape capabilities linked to the viral peptide HA2. In particular, the construct T22-GFP-HA2-H6 forms nanoparticles that upon administration in mouse models of human, CXCR4(+) colorectal cancer, accumulates in primary tumor at levels significantly higher than the parental T22-GFP-H6 HA2-lacking version. The in vivo application of a CXCR4 antagonist has confirmed the prevalence of the CXCR4(+) tumor tissue selectivity over unspecific cell penetration, upon systemic administration of the material. Such specificity is combined with improved endosomal escape, what overall results in a precise and highly efficient tumor biodistribution. These data strongly support the functional recruitment as a convenient approach to generate protein materials for clinical applications. More precisely, they also support the unexpected concept that enhancing the unspecific membrane activity of a protein material does not necessarily compromise, but it can even improve, the selective cell targeting offered by an accompanying functional module.
Statement of Significance
We have shown here that the combination of cell-penetrating and tumor cell-targeting peptides dramatically enhances precise tumor accumulation of protein-only nanoparticles intended for selective drug delivery, in mouse models of human colorectal cancer. This fact is a step forward for the rational design of multifunctional protein nanomaterials for improved cancer therapies. (C) 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Filiaciones:
Sala R:
CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), C/Monforte de Lemos 3-5, 28029 Madrid, Spain
Institut d'Investigacions Biomèdiques Sant Pau and Josep Carreras Research Institute, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain
Sánchez-García L:
CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), C/Monforte de Lemos 3-5, 28029 Madrid, Spain
Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain
Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain
Serna N:
CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), C/Monforte de Lemos 3-5, 28029 Madrid, Spain
Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain
Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain
Céspedes MV:
CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), C/Monforte de Lemos 3-5, 28029 Madrid, Spain
Institut d'Investigacions Biomèdiques Sant Pau and Josep Carreras Research Institute, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain
Casanova I:
CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), C/Monforte de Lemos 3-5, 28029 Madrid, Spain
Institut d'Investigacions Biomèdiques Sant Pau and Josep Carreras Research Institute, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain
Roldan-Molina M:
Unitat de Microscòpia Confocal, Servei d'Anatomia Patològica, Institut Pediàtric de Malalties Rares (IPER), Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain
Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain
Sánchez-Chardi A:
Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, Universitat de Barcelona, 08028 Barcelona, Spain
Unzueta U:
CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), C/Monforte de Lemos 3-5, 28029 Madrid, Spain
Institut d'Investigacions Biomèdiques Sant Pau and Josep Carreras Research Institute, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain
Vázquez E:
CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), C/Monforte de Lemos 3-5, 28029 Madrid, Spain
Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain
Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain
Mangues R:
CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), C/Monforte de Lemos 3-5, 28029 Madrid, Spain
Institut d'Investigacions Biomèdiques Sant Pau and Josep Carreras Research Institute, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain
Villaverde A:
CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), C/Monforte de Lemos 3-5, 28029 Madrid, Spain
Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain
Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain
Green Accepted
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