High-yield halide-assisted synthesis of metal–organic framework UiO-based nanocarriers

The synthesis of nanosized metal–organic frameworks (NMOFs) is requisite for their application as injectable drug delivery systems (DDSs) and other biorelevant purposes. Herein, we have critically examined the role of different synthetic parameters leading to the production of UiO-66 crystals smaller than 100 nm. Of note, we demonstrate the co-modulator role conferred by halide ions, not only to produce NMOFs with precise morphology and size, but also to significantly improve the reaction yield. The resulting NMOFs are highly crystalline and exhibit sustained colloidal stability in different biologically relevant media. As a proof of concept, these NMOFs were loaded with Rhodamine 6G (R6G), which remained trapped in most common biologically relevant media. When incubated with living mammalian cells, the R6G-loaded NMOFs were efficiently internalized and did not impair cell viability even at relatively high doses.The authors acknowledge the financial support of the MCIN/AEI (PID2019-108624RB-I00, RYC-2017-23457, RYC-2019-028238-I), the Xunta de Galicia (ED431F 2017/02, ED431F 2020/11, 2021-CP090, Centro Singular de Investigación de Galicia Accreditation 2019–2022, ED431G 2019/03), the European Union (European RegionalDevelopment Fund – ERDF; H2020-MSCA-ITN grant agreement no. 860942; H2020-FET-Open grant agreement no. 899612; H2020-ICT grant agreement no. 10101694 and INTERREG V-A Spain–Portugal, project 0624_2IQBIONEURO_6_E), and the European Research Council (starting grant no. 950421). M.C.-M. thanks the AEI (FPU19/03155). The authors are grateful for the use of RIAIDT-USC analytical facilities.S