Author(s): Gonçalves, Anabela ; Pinho, Vanessa ; da Costa, André ; Ribeiro, Artur ; Gomes, Andreia C ; Machado, Raul
Date: 2024
Persistent ID: https://hdl.handle.net/1822/93761
Origin: RepositóriUM - Universidade do Minho
Subject(s): Genetics; Nanoparticles; Peptides and proteins; Polymers; Purification
Oncostatin M (OSM) and leukemia inhibitory factor (LIF) are pleiotropic cytokines from the interkeukine-6 family, associated with several disorders, and present significant potential in biomedicine. However, their therapeutic use is highly constrained by factors such as short circulating half-life and narrow therapeutic window. The conjugation of cytokines with elastin-like recombinamers (ELR) holds the potential to circumvent these limitations due to the ability of self-assembling upon a thermal stimulus, remarkable biocompatibility, and ease of processing. In this work, we report on the development of genetically engineered hybrid ELR conjugates by fusing the DNA sequences coding for murine/human OSM and LIF into the C-terminus of an ELR. The resulting hybrid fusion proteins demonstrated to retain the thermal properties of the ELR, which enabled the nonchromatographic purification by employing simple hot/cold cycles. Nanoparticles and free-standing films were obtained by self-assembly and solvent casting, respectively, using environmentally friendly processes (mild conditions and water-based methods). Both materials were characterized for their properties, revealing the absence of hemotoxicity upon contact with red blood cells and promising features for potential therapeutic applications. Overall, this work represents a step forward in the development of advanced functionalized biomaterials suitable for localized cytokine therapy.
