Carrillo Carrión, CarolinaComaills, ValentineVisiga, Ana M.Gauthier, Benoit R.Khiar, Noureddine2024-06-132024-06-132023Carrillo Carrión, C., Comaills, V., Visiga, A.M., Gauthier, B.R. y Khiar, N. (2023). Enzyme-Responsive Zr-Based Metal-Organic Frameworks for Controlled Drug Delivery: Taking Advantage of Clickable PEG-Phosphate Ligands. ACS Applied Materials and Interfaces, 15 (23), 27600-27611. https://doi.org/10.1021/acsami.3c03230.1944-82441944-8252https://hdl.handle.net/11441/160464We 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.application/pdf12 p.engAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/BiocompatibilityClick chemistryControlled drug-releaseEnzyme-responsiveMetal−organic frameworksinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccesshttps://doi.org/10.1021/acsami.3c03230