Bacterial mimetics of endocrine secretory granules as immobilized in vivo depots for functional protein drugs.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Bacteria/*metabolism ; Cytoplasmic Granules/*metabolism ; Endocrine System/*metabolism ; Pharmaceutical Preparations/*metabolism ; Secretory Vesicles/*metabolism; Amyloid/metabolism ; Amyloidogenic Proteins/metabolism ; Animals ; Apoptosis/drug effects ; Biomimetics/methods ; Cell Line, Tumor ; Female ; HT29 Cells ; Humans ; Inclusion Bodies/metabolism ; Mice ; Mice, Nude ; Nanostructures/administration & dosage

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.

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0 (Amyloid)
0 (Amyloidogenic Proteins)
0 (Pharmaceutical Preparations)

Date Created: 20161025 Date Completed: 20180418 Latest Revision: 20181113

20250114

PMC5075894

10.1038/srep35765

27775083