Rui R Costa, Vicente Domínguez-Arca, Brenda Velasco, Rui L Reis, José Carlos Rodríguez-Cabello, Iva Pashkuleva, Pablo Taboada, Gerardo Prieto
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引用次数: 0
Abstract
Current models for elastin-like recombinamer (ELR) design struggle to predict the effects of nonprotein fused materials on polypeptide conformation and temperature-responsive properties. To address this shortage, we investigated the novel functionalization of ELRs with cholesterol (CTA). We employed GROMACS computational molecular dynamic simulations complemented with experimental evidence to validate the in silico predictions. The ELRCTA was biosynthesized and characterized by using fluorescence assays, circular dichroism, dynamic light scattering, and differential scanning calorimetry. The in silico and in vitro data showed that CTA promotes the formation of intramolecular hydrogen bonds that favor β-sheet secondary structures. Compared with an unmodified ELRVKV, CTA enhanced the hydrophobicity and stability of the system, allowing the formation of monodisperse nanoaggregates at physiologically relevant temperatures. Importantly, calorimetry assays revealed that ELRCTA interacted and intercalated with the lipid bilayers of the DPPC liposomes. To demonstrate the implications of these changes for biomedical applications, ELRCTA and DPPC-ELRCTA hybrid nanoparticles were tested with cancer and immune cell lines. Interactions with the cell membranes demonstrated a synergistic effect of the composition and size of the modified recombinamer aggregates on the internalization. The results indicated the potential use of ELR-based nanoparticles for localized and systemic drug delivery. This work sets a new precedent to design elastin-inspired biomaterials with predictable self-assembly properties and develop novel drug delivery strategies.
期刊介绍:
ACS Applied Materials & Interfaces is a leading interdisciplinary journal that brings together chemists, engineers, physicists, and biologists to explore the development and utilization of newly-discovered materials and interfacial processes for specific applications. Our journal has experienced remarkable growth since its establishment in 2009, both in terms of the number of articles published and the impact of the research showcased. We are proud to foster a truly global community, with the majority of published articles originating from outside the United States, reflecting the rapid growth of applied research worldwide.