Phospholipid-inspired alkoxylation induces crystallization and cellular uptake of luminescent COF nanocarriers

The porous nature and structural variability of covalent organic frameworks (COFs) make them preferred for drug loading and delivery applications. However, most COF materials suffer from poor luminescent properties and inefficiency for cell uptake. Herein, we experimentally demonstrate the crucial role of long alkoxy chains in the synthesis of crystalline COF nanostructures with high cellular uptake efficiency. After luminescence integration through band engineering, the semiconducting COF exhibits an optical bandgap of 2.05 eV, an emission wavelength of 632 nm, a high quantum yield of 37 %, and excellent fluorescence stability (100 % at 3 h). Such excellent optical properties of the designed COF nanocarriers enable quantitative evaluations of cellular uptake and visual tracking of drug delivery. It was demonstrated that the cellular uptake efficiency was enhanced by orders of magnitude for the COF after the introduction of long n-octyloxy chains, which firstly delivered the anticancer camptothecin (CPT) to cell lysosomes, and then underwent “endo/lysosomal escape” to induce cell apoptosis. In vivo assay evidenced a significant enhancement in the therapeutic effect with a 96 % inhibition of tumor growth after 14 days of treatment. This progress sheds light on designing cutting-edge drug delivery nanosystems based on COF materials with integrated diagnostic and therapeutic functions.