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This work was financially supported by Spanish MICINN (PID2019-106268GB-C33, TED2021-129886B-C43, PID2020-114755GB-C32, PID2020-113142RB-C21 and PLEC2021-007906), as well as by project PID2021-126304OB-C41 via MCIN/AEI/10.13039/501100011033/, by European Regional Development Fund - A way of doing Europe and by the Generalitat Valenciana (CIPROM/2021/007). J.I.M. also acknowledges funding from EU via the European Graphene Flagship (Grant Graphene Core3 881603) and Comunidad de Madrid (Grants S2018/NMT-4367 and Y2020/NMT-6469)., Covalent organic Frameworks (COFs) are a class of crystalline macromolecular materials build-up by monomers with specific symmetries or functionalities. There are important limitations in the synthesis of highly ordered COFs, such as the shape and packing of the building blocks. Thus, the presence of fluorine atoms that lie perpendicular to the bisecting plane of BODIPY derivatives together with the presence of four bulky methyl groups could hinder the crystallization process in COF synthesis. For that reason, BODIPY-based COFs are rarely incorporated to COF networks. In this work, following the mixed linker strategy, a pre-synthetic method to dope COF structures with BODIPY units was developed. The materials have been processed into fluorescent Covalent Organic Nanosheets (CONs) with defined particle-size distributions around 100 nm, suitable for cellular biomedical applications. The viability of the CONs was evaluated using Sk-Mel-103 cells, demonstrating the internalization showing 100% cell viability. We envisage that this work could accelerate the discovery of new COF-based materials for biomedical sciences, MICINN, Generalitat Valenciana, Comunidad de Madrid, Depto. de Química Orgánica, Fac. de Ciencias Químicas, TRUE, pub

[EN] Covalent organic Frameworks (COFs) are a class of crystalline macromolecular materials build-up by monomers with specific symmetries or functionalities. There are important limitations in the synthesis of highly ordered COFs, such as the shape and packing of the building blocks. Thus, the presence of fluorine atoms that lie perpendicular to the bisecting plane of BODIPY derivatives together with the presence of four bulky methyl groups could hinder the crystallization process in COF synthesis. For that reason, BODIPY-based COFs are rarely incorporated to COF networks. In this work, following the mixed linker strategy, a pre-synthetic method to dope COF structures with BODIPY units was developed. The materials have been processed into fluorescent Covalent Organic Nanosheets (CONs) with defined particle-size distributions around 100 nm, suitable for cellular biomedical applications. The viability of the CONs was evaluated using Sk-Mel-103 cells, demonstrating the internalization showing 100% cell viability. We envisage that this work could accelerate the discovery of new COF-based materials for biomedical sciences.