title: Bacterial mimetics of endocrine secretory granules as immobilized in vivo depots for functional protein drugs.
abstract: In the human endocrine system many protein hormones including urotensin, glucagon, obestatin, bombesin and secretin, among others, are supplied from amyloidal secretory granules. These granules form part of the so called functional amyloids, which within the whole aggregome appear to be more abundant than formerly believed. Bacterial inclusion bodies (IBs) are non-toxic, nanostructured functional amyloids whose biological fabrication can be tailored to render materials with defined biophysical properties. Since under physiological conditions they steadily release their building block protein in a soluble and functional form, IBs are considered as mimetics of endocrine secretory granules. We have explored here if the in vivo implantation of functional IBs in a given tissue would represent a stable local source of functional protein. Upon intratumoral injection of bacterial IBs formed by a potent protein ligand of CXCR4 we have observed high stability and prevalence of the material in absence of toxicity, accompanied by apoptosis of CXCR4+cells and tumor ablation. Then, the local immobilization of bacterial amyloids formed by therapeutic proteins in tumors or other tissues might represent a promising strategy for a sustained local delivery of protein drugs by mimicking the functional amyloidal architecture of the mammals' endocrine system.
authors: Institut d'Investigacions Biomèdiques Sant Pau and Josep Carreras Research Institute, Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain.|CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain.
authors: María Virtudes
authors: MV
authors: Céspedes
authors: CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain.|CIBBIM-Nanomedicine, Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, 08035, Barcelona, Spain.
authors: Yolanda
authors: Y
authors: Fernández
authors: Institut d'Investigacions Biomèdiques Sant Pau and Josep Carreras Research Institute, Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain.|CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain.
authors: Ugutz
authors: U
authors: Unzueta
authors: CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain.|Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain.
authors: Rosa
authors: R
authors: Mendoza
authors: CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain.|CIBBIM-Nanomedicine, Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, 08035, Barcelona, Spain.
authors: Joaquin
authors: J
authors: Seras-Franzoso
authors: Servei de Microscòpia, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain.
authors: Alejando
authors: A
authors: Sánchez-Chardi
authors: Institut d'Investigacions Biomèdiques Sant Pau and Josep Carreras Research Institute, Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain.|CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain.
authors: Patricia
authors: P
authors: Álamo
authors: CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 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.
authors: Verónica
authors: V
authors: Toledo-Rubio
authors: CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 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.
authors: Neus
authors: N
authors: Ferrer-Miralles
authors: Institut d'Investigacions Biomèdiques Sant Pau and Josep Carreras Research Institute, Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain.|CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain.
authors: Esther
authors: E
authors: Vázquez
authors: CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain.|CIBBIM-Nanomedicine, Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, 08035, Barcelona, Spain.
authors: Simó
authors: S
authors: Schwartz
authors: CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain.|CIBBIM-Nanomedicine, Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, 08035, Barcelona, Spain.
authors: Ibane
authors: I
authors: Abasolo
authors: CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 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.
authors: José Luis
authors: JL
authors: Corchero
authors: Institut d'Investigacions Biomèdiques Sant Pau and Josep Carreras Research Institute, Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain.|CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain.
authors: Ramon
authors: R
authors: Mangues
authors: CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 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.
authors: Antonio
authors: A
authors: Villaverde
mesh_terms: D000682:Amyloid / Q000378:metabolism; D058227:Amyloidogenic Proteins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001419:Bacteria / Q000378:metabolism*; D032701:Biomimetics / Q000379:methods; D045744:Cell Line, Tumor; D003594:Cytoplasmic Granules / Q000378:metabolism*; D004703:Endocrine System / Q000378:metabolism*; D005260:Female; D019073:HT29 Cells; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D049329:Nanostructures / Q000008:administration & dosage; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D022142:Secretory Vesicles / Q000378:metabolism*
chemical_list: D000682:Amyloid; D058227:Amyloidogenic Proteins; D004364:Pharmaceutical Preparations