Engineering Secretory Amyloids for Remote and Highly Selective Destruction of Metastatic Foci

Autor: Céspedes, María Virtudes, Cano-Garrido, Olivia, Álamo, Patricia, Sala, Rita, Gallardo, Alberto, Serna, Naroa, Falgàs, Aïda, Voltà-Durán, Eric, Casanova Rigat, Isolda, Sánchez Chardi, Alejandro, López-Laguna, Hèctor, Sánchez-García, Laura, Sanchez, Julieta M., Unzueta Elorza, Ugutz, Vázquez Gómez, Esther, Mangues, Ramon, Villaverde Corrales, Antonio, Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia
Rok vydání: 2019
Předmět:
Amyloid
Receptors
CXCR4
Materials science
Cell Survival
Molecular Conformation
Exotoxins
Antineoplastic Agents
Apoptosis
02 engineering and technology
010402 general chemistry
Protein Engineering
01 natural sciences
CXCR4
Inclusion bodies
Chemokine receptor
Mice
metastatic cancer
Bacterial Proteins
Cancer stem cell
In vivo
protein materials
Pseudomonas exotoxin
Animals
Humans
General Materials Science
Secretion
Molecular Targeted Therapy
Neoplasm Metastasis
drug release
Inclusion Bodies
Drug Carriers
Mechanical Engineering
secretory amyloids
self-assembly
021001 nanoscience & nanotechnology
In vitro
Recombinant Proteins
0104 chemical sciences
Drug Liberation
Mechanics of Materials
Cancer research
Neoplastic Stem Cells
Nanoparticles
0210 nano-technology
Colorectal Neoplasms
Peptides
HeLa Cells
Zdroj: ADVANCED MATERIALS
r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname
Dipòsit Digital de Documents de la UAB
Universitat Autònoma de Barcelona
ISSN: 1521-4095
0935-9648
Popis: Altres ajuts: to EU COST Action CA 17140 Functional amyloids produced in bacteria as nanoscale inclusion bodies are intriguing but poorly explored protein materials with wide therapeutic potential. Since they release functional polypeptides under physiological conditions, these materials can be potentially tailored as mimetic of secretory granules for slow systemic delivery of smart protein drugs. To explore this possibility, bacterial inclusion bodies formed by a self-assembled, tumor-targeted Pseudomonas exotoxin (PE24) are administered subcutaneously in mouse models of human metastatic colorectal cancer, for sustained secretion of tumor-targeted therapeutic nanoparticles. These proteins are functionalized with a peptidic ligand of CXCR4, a chemokine receptor overexpressed in metastatic cancer stem cells that confers high selective cytotoxicity in vitro and in vivo. In the mouse models of human colorectal cancer, time-deferred anticancer activity is detected after the subcutaneous deposition of 500 µg of PE24-based amyloids, which promotes a dramatic arrest of tumor growth in the absence of side toxicity. In addition, long-term prevention of lymphatic, hematogenous, and peritoneal metastases is achieved. These results reveal the biomedical potential and versatility of bacterial inclusion bodies as novel tunable secretory materials usable in delivery, and they also instruct how therapeutic proteins, even with high functional and structural complexity, can be packaged in this convenient format.
Databáze: OpenAIRE
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