2 research outputs found

    In vitro fabrication of microscale secretory granules

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    Advanced medical treatments involving drug delivery require fully biocompatible materials with the ability to release functional drugs in a time-prolonged way. Ideally, the delivered molecules should be self-contained as chemically homogenous entities to prevent the use of potentially toxic scaffolds or hold matrices. In nature, peptidic hormones are self-stored in protein-only secretory granules formed by the reversible coordination of Zn2+ and histidine residues. Inspired by this concept, an in vitro transversal procedure is developed, analyzed, and comparatively applied for the fabrication of protein-only secretory granules at the microscale. These materials can be produced from any polyhistidine-tagged protein using physiological concentrations of Zn2+ as a potent and versatile glue-like agent. The screening of granules formed by 12 engineered and nonengineered proteins at different Zn2+ concentrations revealed optimal fabrication conditions and the consequent release profiles. Moreover, the functional and structural properties of the delivered protein are fully validated using a drug-targeting protein platform in a mouse model of human colorectal cancer. In summary, short histidine tags allow the packaging of structurally and functionally dissimilar polypeptides, which supports the proposed fabrication method as a powerful protocol extensible to diverse clinical scenarios in which slow protein drug delivery is required.Fil: Hector Lopez Laguna. Universitat Autònoma de Barcelona; EspañaFil: Eloi Parlade. Universitat Autònoma de Barcelona; EspañaFil: Patricia Álamo,. Hospital de la Santa Creu I Sant Pau; EspañaFil: Sanchez, Julieta Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Eric Volta Duran. Universitat Autònoma de Barcelona; EspañaFil: Naroa Serna. Universitat Autònoma de Barcelona; EspañaFil: Laura Sánchez-Garcia. Universitat Autònoma de Barcelona; EspañaFil: Olivia Cano-Garrido. Universitat Autònoma de Barcelona; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Alejandro Sánchez-Chardi. Universitat Autònoma de Barcelona; EspañaFil: Antonio Villaverde. Universitat Autònoma de Barcelona; EspañaFil: Ramon Mangues. Hospital de la Santa Creu I Sant Pau; EspañaFil: Ugutz Unzueta. Hospital de la Santa Creu I Sant Pau; EspañaFil: Esther Vázquez. Universitat Autònoma de Barcelona; Españ
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