Elastin-like Polymers as Nanovaccines: Protein Engineering of Self-Assembled, Epitope-Exposing Nanoparticles

Girotti, Alessandra; González‐Valdivieso, Juan; Alonso-Sampedro, Irene; Escalera-Anzola, Sara; Ramos-Díez, Sandra; Arias, Francisco J.

doi:10.1007/978-1-0716-2168-4_3

Cited by 2 publications

(2 citation statements)

References 28 publications

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“…Protein-based NPs can be fabricated with many methods, including desolvation, coacervation, self-assembly, thermal gelation, spray-drying, emulsification, and chemical crosslinking. [63][64][65][66] During particle formation, proteins undergo conformational changes depending on the composition and concentration of protein. Other environmental factors also play an important role in NP formation, such as solution pH, temperature, stirring rate, ionic strength, ratios of chemical agents, and crosslinking method, all of which influences the size, electrostatic interactions, surface charge, and stability of the final particles.…”

Section: Discussionmentioning

confidence: 99%

From bone to nanoparticles: development of a novel generation of bone derived nanoparticles for image guided orthopedic regeneration

Stellpflug,

Walls,

Hansen

et al. 2024

Biomater. Sci.

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Section: Discussionmentioning

confidence: 99%

From bone to nanoparticles: development of a novel generation of bone derived nanoparticles for image guided orthopedic regeneration

Stellpflug,

Walls,

Hansen

et al. 2024

Biomater. Sci.

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“…In addition, ELRs allow to precisely control their molecular weight, functionality, and mechanical properties by modifying their amino acid sequence at will. ELRs are now investigated for diverse biomedical applications, particularly in drug delivery [26], nanovaccines [27], but also as biocompatible stent-coating to improve the success of angioplasty [28,29], or more recently for the engineering of venous valves [30] just to cite a few. As a matter of fact, products inspired by elastin are exclusively used as building blocks in the formulation of biomaterials, either a vehicle or a scaffold for tissue engineering.…”

Section: Introductionmentioning

confidence: 99%

A synthetic elastic protein as molecular prosthetic candidate to strengthen vascular wall elasticity

Hoareau,

Lorion,

Lecoq

et al. 2023

Preprint

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The loss of elasticity is a hallmark of systemic aging or genetic syndromes (e.g. cutis laxa, Williams-Beuren and supravalvular aortic stenosis) with direct consequences on tissue functions, and particularly deleterious when associated to the cardiovascular system. Tissue elasticity is mainly provided by large elastic fibers composed of supramolecular complexes of elastin and microfibrils. In arteries, the mature elastic fibers are located in the media compartment and form concentric elastic lamellar units together with the smooth muscle cells (SMCs). The main function of vascular elastic fibers is to allow extension and recoil of the vessel walls in response to the intraluminal pressure generated by the blood flow following cardiac systole. The synthesis of elastic fibers (elastogenesis) mainly occurs during the last third of fetal life with a peak in the perinatal period and then slowly decreases until the end of growth; as a result, elastic fiber repair is almost non-existent in adults. To date, no treatment exists to restore or repair deficient or degraded elastic fibers. A few pharmacological compounds have been proposed, but their efficacy/side effects balance remains very unfavorable. As an alternative strategy, we developed a synthetic elastic protein (SEP) inspired by the human tropoelastin, the elastin soluble precursor, to provide an elastic molecular prosthesis capable of integrating and reinforcing endogenous elastic fibers.The SEP was easily produced in E. coli and purified by inversed transition cycling method. The resulting 55 kDa protein recapitulates the main physicochemical properties of the tropoelastin as thermal responsiveness, intrinsically disordered structures, and spherical self-assembly. The cross-linked SEP displays linear elastic mechanical properties under uniaxial tension loads. Using a co-culturein vitromodel of the endothelial barrier, our results show that SEP is able to cross the cohesive endothelial monolayer to reach underlying SMCs. Moreover, SEP is processed by SMCs through a lysyl oxidase-dependent mechanism to form fibrillar structures that colocalize with fibrillin-rich microfibrils. The SEP was further characterizedin vivothrough the zebrafish model. The results indicate a global innocuity on zebrafish embryos and an absence of neutrophil recruitment following injection into the yolk sac of zebrafish. Finally, intravenous injection of a fluorescent SEP highlights its deposition in the wall of tortuous vessels which persists for several days after injection of the larvae. Taken together, our results demonstrate for the first time the incorporation of a naked tropoelastin-bioinspired polypeptide in endogenous elastic fibrillar deposits from SMCs, and its recognition by the lysyl- oxidase enzymatic machinery. In absence of toxicity and proinflammatory signal combined to a long-lasting accumulation in vesselsin vivo, the SEP fulfills the first prerequisites for the development of an original biotherapeutic compound addressing the repair of elastic fibers.

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Elastin-like Polymers as Nanovaccines: Protein Engineering of Self-Assembled, Epitope-Exposing Nanoparticles

Cited by 2 publications

References 28 publications

From bone to nanoparticles: development of a novel generation of bone derived nanoparticles for image guided orthopedic regeneration

From bone to nanoparticles: development of a novel generation of bone derived nanoparticles for image guided orthopedic regeneration

A synthetic elastic protein as molecular prosthetic candidate to strengthen vascular wall elasticity

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