Biología Celular

URI permanente para esta comunidadhttps://hdl.handle.net/11441/10813

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Examinando Biología Celular por Agencia financiadora "Asociación Española Contra el Cáncer"

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    Enzyme-Responsive Zr-Based Metal-Organic Frameworks for Controlled Drug Delivery: Taking Advantage of Clickable PEG-Phosphate Ligands
    (American Chemical Society, 2023) Carrillo Carrión, Carolina; Comaills, Valentine; Visiga, Ana M.; Gauthier, Benoit R.; Khiar, Noureddine; Universidad de Sevilla. Departamento de Biología Celular; Ministerio de Ciencia, Innovación y Universidades (MICINN). España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Junta de Andalucía; Asociación Española Contra el Cáncer; Marie Sklodowska-Curie Individual Fellowship; European Cooperation in Science and Technology (COST)
    We report for the first time the controlled drug release from a nanoscale Zr-based metal-organic framework (MOF), UiO-66, in the presence of the enzyme alkaline phosphatase (ALP). This unprecedented reactivity was possible thanks to the prior functionalization of the MOF with N3-PEG-PO3 ligands, which were designed for three specific aims: (1) to impart colloidal stability in phosphate-containing media; (2) to endow the MOF with multifunctionality thanks to azide groups for the covalent attachment of an imaging agent by click-chemistry; and (3) to confer stimuli-responsive properties, specifically the selective release of doxorubicin triggered by the enzymatic activity of ALP. Cell studies revealed that the functionalization of the MOF with N3-(PEG)20-PO3 ligands improved their intracellular stability and led to a sustained drug release compared to the bare MOF. More importantly, an enhanced drug release was observed in cells with higher expression of ALP genes (HeLa versus MDA-MB-231 and MCF7), confirming the ALP-responsiveness of the system inside living cells.