Lyophilization of biomimetic amyloids preserves their regulatable, endocrine-like functions for nanoparticle release
Por:
Favaro, MTP, López-Laguna, H, Voltà-Durán, E, Alba-Castellon, L, Sánchez, JM, Casanova, I, Unzueta, U, Mangues, R, Villaverde, A and Vázquez, E
Publicada:
1 ago 2024
Ahead of Print:
1 jul 2024
Resumen:
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.
Filiaciones:
Favaro, MTP:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Bellaterra 08193, Spain
López-Laguna, H:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Bellaterra 08193, Spain
Univ Autonoma Barcelona, CIBER Bioingn Biomat & Nanomed CIBER BBN, ISCIII, Bellaterra 08193, Spain
Voltà-Durán, E:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Bellaterra 08193, Spain
Univ Autonoma Barcelona, CIBER Bioingn Biomat & Nanomed CIBER BBN, ISCIII, Bellaterra 08193, Spain
Alba-Castellon, L:
Univ Autonoma Barcelona, CIBER Bioingn Biomat & Nanomed CIBER BBN, ISCIII, Bellaterra 08193, Spain
Inst Recerca St Pau IR St Pau, St Quinti 77-79, Barcelona 08041, Spain
Josep Carreras Leukaemia Res Inst, Barcelona 08025, Spain
Sánchez, JM:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Bellaterra 08193, Spain
Univ Autonoma Barcelona, CIBER Bioingn Biomat & Nanomed CIBER BBN, ISCIII, Bellaterra 08193, Spain
Univ Nacl Cordoba, Fac Ciencias Exactas Fis & Nat, Dept Quim, Catedra Quim Biol,ICTA, Ave Velez Sarsfield 1611, RA-5016 Cordoba, Argentina
Univ Nacl Cordoba, Inst Invest Biol & Tecnol IIByT, CONICET, RA-5016 Cordoba, Argentina
:
Univ Autonoma Barcelona, CIBER Bioingn Biomat & Nanomed CIBER BBN, ISCIII, Bellaterra 08193, Spain
Inst Recerca St Pau IR St Pau, St Quinti 77-79, Barcelona 08041, Spain
Josep Carreras Leukaemia Res Inst, Barcelona 08025, Spain
:
Univ Autonoma Barcelona, CIBER Bioingn Biomat & Nanomed CIBER BBN, ISCIII, Bellaterra 08193, Spain
Inst Recerca St Pau IR St Pau, St Quinti 77-79, Barcelona 08041, Spain
Josep Carreras Leukaemia Res Inst, Barcelona 08025, Spain
:
Univ Autonoma Barcelona, CIBER Bioingn Biomat & Nanomed CIBER BBN, ISCIII, Bellaterra 08193, Spain
Inst Recerca St Pau IR St Pau, St Quinti 77-79, Barcelona 08041, Spain
Josep Carreras Leukaemia Res Inst, Barcelona 08025, Spain
Villaverde, A:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Bellaterra 08193, Spain
Univ Autonoma Barcelona, CIBER Bioingn Biomat & Nanomed CIBER BBN, ISCIII, Bellaterra 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Bellaterra 08193, Spain
Vázquez, E:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Bellaterra 08193, Spain
Univ Autonoma Barcelona, CIBER Bioingn Biomat & Nanomed CIBER BBN, ISCIII, Bellaterra 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Bellaterra 08193, Spain
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