TY - JOUR
T1 - Lyophilization of biomimetic amyloids preserves their regulatable, endocrine-like functions for nanoparticle release
AU - de Pinho Favaro, Marianna T
AU - López-Laguna, Hèctor
AU - Voltà-Durán, Eric
AU - Alba-Castellón, Lorena
AU - Sánchez, Julieta M.
AU - Casanova, Isolda
AU - Unzueta Elorza, Ugutz
AU - Mangues, Ramon
AU - Villaverde Corrales, Antonio
AU - Vázquez Gómez, Esther
N1 - Publisher Copyright:
© 2024 The Author(s)
PY - 2024/8
Y1 - 2024/8
N2 - The secretory granules from the mammalian endocrine system are functional amyloids that act as dynamic depots to store and release protein hormones into the bloodstream. The controlled in vitro coordination between divalent cations and solvent-exposed histidine residues triggers reversible, cross-molecular interactions that result in granular protein aggregates with protein-leaking properties. While these synthetic particles are mechanically stable, they progressively disintegrate and release their protein building blocks, mimicking the performance of secretory granules. Envisaged as delivery systems for endocrine-like, time-sustained protein release, their clinical applicability should be supported by robust storage procedures, so far unset. Being lyophilization a desirable storage method for protein drugs, how this procedure could preserve the performance of clinically oriented functional amyloids is a neglected issue. We have here explored, tailored and validated lyophilization as an industrially and clinically friendly, fully scalable approach to the storage of functional amyloids aimed at secretion of protein-only nanoparticles. By doing so, protein-protein interactions in such materials have been characterized, and citrate identified as an efficient modulator of the temporal secretion profile, through which the sustainability of the leaking process can be finely regulated.
AB - The secretory granules from the mammalian endocrine system are functional amyloids that act as dynamic depots to store and release protein hormones into the bloodstream. The controlled in vitro coordination between divalent cations and solvent-exposed histidine residues triggers reversible, cross-molecular interactions that result in granular protein aggregates with protein-leaking properties. While these synthetic particles are mechanically stable, they progressively disintegrate and release their protein building blocks, mimicking the performance of secretory granules. Envisaged as delivery systems for endocrine-like, time-sustained protein release, their clinical applicability should be supported by robust storage procedures, so far unset. Being lyophilization a desirable storage method for protein drugs, how this procedure could preserve the performance of clinically oriented functional amyloids is a neglected issue. We have here explored, tailored and validated lyophilization as an industrially and clinically friendly, fully scalable approach to the storage of functional amyloids aimed at secretion of protein-only nanoparticles. By doing so, protein-protein interactions in such materials have been characterized, and citrate identified as an efficient modulator of the temporal secretion profile, through which the sustainability of the leaking process can be finely regulated.
KW - Functional amyloids
KW - Recombinant proteins
KW - Dynamic protein depots
KW - Endocrine-like function
KW - Drug delivery
UR - http://www.scopus.com/inward/record.url?scp=85199412970&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/317ede9f-b7f7-3e21-af87-3bf66169c505/
U2 - 10.1016/j.apmt.2024.102348
DO - 10.1016/j.apmt.2024.102348
M3 - Article
SN - 2352-9407
VL - 39
JO - Applied Materials Today
JF - Applied Materials Today
M1 - 102348
ER -