Year: 2025
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide The mammalian endocrine system uses functional amyloids as dynamic depots to store and release protein hormones into the bloodstream. Such depots, acting as secretory granules within the microscale, are formed in specialized cells by the coordination between the ionic, divalent form of zinc (Zn 2+ ) and the imidazole ring from accessible His residues. The reversibility of such cross-linking events allows for the release of monomeric or oligomeric forms of the functional protein for biological activity. In vitro, and mimicking such a natural coordination process, synthetic amyloidal granules with secretory properties can be fabricated using selected therapeutic proteins as building blocks. Then, these microparticles act as delivery systems for endocrine-like, sustained protein release, with proven applicability in vaccinology, cancer therapy, regenerative medicine, and as antimicrobial agents. While the temporal profile in which the protein is leaked from the material might be highly relevant to clinically oriented applications, the fine control of such parameters remains unclear. We have explored here how the kinetics of protein release can be regulated by intervening in the storage formulation of the granules, through the concentration of citrate not only as a buffer component and protein stabilizer but also as a chelating agent. The citrate-assisted, time-prolonged regulatable release of proteins, in their functional form, opens a spectrum of possibilities to adjust the preparation of synthetic secretory granules to specific clinical needs.
Institutions: Universitat Autònoma de Barcelona, Instituto de Salud Carlos III, Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine, Centro de Investigación Biomédica en Red, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Nacional de Córdoba, Institut de Recerca Sant Pau
Language: English
Subfield: Biomaterials
Field: Materials Science
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Funders: Ministerio de Ciencia, Innovación y Universidades, Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina, Agència de Gestió d'Ajuts Universitaris i de Recerca, Instituto de Salud Carlos III, European Regional Development Fund, Agencia Estatal de Investigación, National Institute of General Medical Sciences, NextGenerationEU
Awards: G1568644027, G1981218610, G3143460420, Eliminación selectiva de células madre metastásicas del cáncer colorrectal por bloqueo de la RNA polimerasa II., G419168934, G4746608580, G575095112, Conjugación dirigida de nanomedicinas proteicas inteligentes para la mejora de la terapia selectiva del cáncer metastasico de colon., G7541801684, G8615798461, G962697420
OpenAlex ID: W4407952787