Lyophilization of biomimetic amyloids preserves their regulatable, endocrine-like functions for nanoparticle release

Marianna T de Pinho Favaro, Hèctor López-Laguna, Eric Voltà-Durán, Lorena Alba-Castellón, Julieta M. Sánchez, Isolda Casanova, Ugutz Unzueta Elorza, Ramon Mangues, Antonio Villaverde Corrales, Esther Vázquez Gómez

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.
Original languageEnglish
Article number102348
Number of pages14
JournalApplied Materials Today
Volume39
DOIs
Publication statusPublished - Aug 2024

Keywords

  • Functional amyloids
  • Recombinant proteins
  • Dynamic protein depots
  • Endocrine-like function
  • Drug delivery

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