Artificial Inclusion Bodies for Clinical Development

JULIETA M. SANCHEZ; HECTOR LOPEZ LAGUNA; PATRICIA ÁLAMO,; NAROA SERNA; ALEJANDRO SÁNCHEZ-CHARDI; VERONICA NOLAN; OLIVIA CANO-GARRIDO; ISOLDA CASANOVA,; UGUTZ UNZUETA ,; ESTHER VÁZQUEZ; RAMON MANGUES; ANTONIO VILLAVERDE

Advanced Science

WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Lugar: Weinheim; Año: 2019

Bacterial inclusion bodies (IBs) are mechanically stable protein particles inthe microscale, which behave as robust, slow protein-releasing amyloids.Upon exposure to cultured cells or upon subcutaneous or intratumor injection,these protein materials secrete functional IB polypeptides, functionallymimicking the endocrine release of peptide hormones from secretoryamyloid granules. Being appealing as delivery systems for prolonged proteindrug release, the development of IBs toward clinical applications is, however,severely constrained by their bacterial origin and by the undefined andprotein-to-protein, batch-to-batch variable composition. In this context, the denovo fabrication of artificial IBs (ArtIBs) by simple, cell-free physicochemicalmethods, using pure components at defined amounts is proposed here. Bythis, the resulting functional protein microparticles are intriguing, chemicallydefined biomimetic materials that replicate relevant functionalities of naturalIBs, including mammalian cell penetration and local or remote release offunctional ArtIB-forming protein. In default of severe regulatory issues, theconcept of ArtIBs is proposed as a novel exploitable category of biomaterialsfor biotechnological and biomedical applications, resulting from simple fabricationand envisaging soft developmental routes to clinics