Small Molecule‐Based Fluorescent Organic Nanoassemblies with Strong Hydrogen Bonding Networks for Fine Tuning and Monitoring Drug Delivery in Cancer Cells

Bright supramolecular fluorescent organic nanoassemblies (FONs), based on strongly polar red‐emissive benzothiadiazole fluorophores containing acidic units, are fabricated to serve as theranostic tools with large colloidal stability in the absence of a polymer or surfactant. High architectural cohesion is ensured by the multiple hydrogen‐bonding networks, reinforced by the dipolar and hydrophobic interactions developed between the dyes. Such interactions are harnessed to ensure high payload encapsulation and efficient trapping of hydrophobic and hydrogen‐bonding drugs like doxorubicin, as shown by steady state and time‐resolved measurements. Fine tuning of the drug release in cancer cells is achieved by adjusting the structure and combination of the fluorophore acidic units. Notably delayed drug delivery is observed by confocal microscopy compared to the entrance of hydrosoluble doxorubicin, demonstrating the absence of undesirable burst release outside the cells by using FONs. Since FON‐constituting fluorophores exhibit a large emission shift from red to green when dissociating in contact with the lipid cellular content, drug delivery could advantageously be followed by dual‐color spectral detection, independently of the drug staining potentiality.