Drug loading strategies for discotic amphiphile supramolecular polymers in water

BTA-based supramolecular polymers are interesting systems for medical applications because of their high dynamicity and stimuli responsiveness in water [1]. Rece ntly, IBEC developed a new class of BTA based supramolecular polymers which showed responsiveness to temperature, salt concentration, pH, and light [2]. This versatility makes this new class of self assembled fibers appealing for drug delivery purposes. In t his work, we explored two strategies to incorporate different biologically active ligands into these polymers and demonstrate their employability as light driven drug delivery systems . In the first strategy, we used a co assembly approach in which two new discotic BTA azo monomers assemble forming the final helicoidal supramolecular fibers. In the second one, we decided to cage Photoiperoxo 3 , a potent photoswitchable derivative of the mAChR agonist Iperoxo [3]. Here, the interaction is based on the stacking between the azobenzene units of the ligand and the monomers. From the first approach, we obtained satisfying co assemby results which were evaluated by transmission electron microscopy. Remarkably, the second system showed light dependent biological effect s in calcium imaging experiments on cells overexpressing M1 mAChRs. While caged Photoiperoxo did not evoke significant changes, UV pre illuminated fibers caused an increase in intracellular calcium levels because of the activation of M1 mAChRs by the uncag ed ligand. These results suggest that the new class of BTA based supramolecular polymers 2 can potentially be used as light driven drug delivery system for small, planar and amphiphilic drugs. References [1] Kantekin, S.; de Greef, T.F.A.; Palmans, A.R.A. Chemical Society Reviews. 41, 6125-6137, (2012). [2] Fuentes E.; Gerth M.; Berrocal J.A.; Matera C.; Gorostiza P.; Voets I.K.; Pujals S.; Albertazzi L. J Am Chem Soc., 142, 10069-10078, (2020). [3] Agnetta, L.; Bermudez, M.; Riefolo, F.; Matera, C.; Claro, E.; Messerer, R.; Littmann, T.; Wolber, G.; Holzgrabe, U.; Decker, M. Journal of Medicinal Chemistry., 62, 3009-3020, (2019).