Supramolecular Assembly of Adamantane-Functionalized BODIPY and Polylactide-Cyclodextrin Conjugate

The combination of beta-cyclodextrin (CD) with biocompatible polymers, such as polylactide (PLA) and its copolymers, generates biomaterials endowed with unique properties due to the synergy of the starting components. PLA-CD derivatives have been fruitfully employed for the development of different types of drug delivery systems, including nanoparticles, microparticles, fibers or hydrogels.[1] One of the main challenges in this area is the monitoring of the in vitro cellular uptake and intracellular trafficking of drug nanocarriers. Among the multitude of highly fluorescent dyes, dipyrromethene boron difluoride (BODIPY) and its derivatives, due to their attractive spectral features, such as high absorption coefficient, high fluorescence quantum yield, and longwavelength emission, have immensely grown in popularity. From the synthetic point of view, the ever-increasing successful applications of BODIPY can be credited to the wide versatility of synthetic pathways to BODIPY derivatives that allows the creation of a perfect fit between the dye structure and the chemical features.[2,3] The conjugation of BODIPY with an adamantane unit (Ada) by a suitable linker chain allows to exploit the well-known supramolecular host-guest interactions between Ada and CD.[4,5] Starting from this concept, we have designed and synthetized a novel adamantane-functionalized BODIPY (Ada-BODIPY) to be included by supramolecular interactions into a polylactide-cyclodextrin conjugate (PLA-CD) conceived as drug delivery system. The newly designed PLA-CD@Ada-BODIPY was prepared by a proper combination of copper-catalyzed click reaction and host-guest interaction.