TY - JOUR
T1 - In Vitro Fabrication of Microscale Secretory Granules
AU - López‐Laguna, Hèctor
AU - Parladé, Eloi
AU - Álamo, Patricia
AU - Sánchez, Julieta M.
AU - Voltà‐Durán, Eric
AU - Serna, Naroa
AU - Sánchez‐García, Laura
AU - Cano‐Garrido, Olivia
AU - Sánchez‐Chardi, Alejandro
AU - Villaverde, Antonio
AU - Mangues, Ramón
AU - Unzueta, Ugutz
AU - Vázquez, Esther
N1 - Publisher Copyright:
© 2021 Wiley-VCH GmbH
PY - 2021/5/17
Y1 - 2021/5/17
N2 - Advanced medical treatments involving drug delivery require fully biocompatible materials with the ability to release functional drugs in a time-prolonged way. Ideally, the delivered molecules should be self-contained as chemically homogenous entities to prevent the use of potentially toxic scaffolds or hold matrices. In nature, peptidic hormones are self-stored in protein-only secretory granules formed by the reversible coordination of Zn
2+ and histidine residues. Inspired by this concept, an in vitro transversal procedure is developed, analyzed, and comparatively applied for the fabrication of protein-only secretory granules at the microscale. These materials can be produced from any polyhistidine-tagged protein using physiological concentrations of Zn
2+ as a potent and versatile glue-like agent. The screening of granules formed by 12 engineered and nonengineered proteins at different Zn
2+ concentrations revealed optimal fabrication conditions and the consequent release profiles. Moreover, the functional and structural properties of the delivered protein are fully validated using a drug-targeting protein platform in a mouse model of human colorectal cancer. In summary, short histidine tags allow the packaging of structurally and functionally dissimilar polypeptides, which supports the proposed fabrication method as a powerful protocol extensible to diverse clinical scenarios in which slow protein drug delivery is required.
AB - Advanced medical treatments involving drug delivery require fully biocompatible materials with the ability to release functional drugs in a time-prolonged way. Ideally, the delivered molecules should be self-contained as chemically homogenous entities to prevent the use of potentially toxic scaffolds or hold matrices. In nature, peptidic hormones are self-stored in protein-only secretory granules formed by the reversible coordination of Zn
2+ and histidine residues. Inspired by this concept, an in vitro transversal procedure is developed, analyzed, and comparatively applied for the fabrication of protein-only secretory granules at the microscale. These materials can be produced from any polyhistidine-tagged protein using physiological concentrations of Zn
2+ as a potent and versatile glue-like agent. The screening of granules formed by 12 engineered and nonengineered proteins at different Zn
2+ concentrations revealed optimal fabrication conditions and the consequent release profiles. Moreover, the functional and structural properties of the delivered protein are fully validated using a drug-targeting protein platform in a mouse model of human colorectal cancer. In summary, short histidine tags allow the packaging of structurally and functionally dissimilar polypeptides, which supports the proposed fabrication method as a powerful protocol extensible to diverse clinical scenarios in which slow protein drug delivery is required.
KW - divalent cations
KW - drug release
KW - microparticles
KW - protein materials
KW - secretory granules
UR - http://www.scopus.com/inward/record.url?scp=85102553034&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/ab7e31ea-fc4b-3685-a139-5ba37415dd46/
U2 - 10.1002/adfm.202100914
DO - 10.1002/adfm.202100914
M3 - Article
SN - 1616-301X
VL - 31
JO - Advanced Functional Materials
JF - Advanced Functional Materials
IS - 21
ER -