Tunable nanogels by host–guest interaction with carboxylate pillar[5]arene for controlled encapsulation and release of doxorubicin

Nanogels have become one of the most attractive systems for application as delivery vectors or for theragnostic approaches in nanomedicine, which is mainly related to the ease of their synthesis by precipitation polymerization. However, only a few suitable monomers have been reported so far and stabilization of the nanogels requires the incorporation of rather defined amounts of in most cases charged co-monomers, such as acrylic acid, which limits the flexibility in their design. Here, we present an alternative approach using a pyridinium based monomer, which not only provides stability due to the positive charge, but also allows the attachment of functional carboxylate-pillar[5]arene by the formation of a host-guest complex. This approach is tested on pH-sensitive nanogels based on the monomer N-[(2,2-dimethyl-1,3-dioxolane)methyl]acrylamide (DMDOMA) featuring an acetal group, which is hydrolysed under acidic conditions. As carboxylates are known to catalyze this hydrolysis, we tested different amounts of carboxylate-pillar[5]arenes to tune the hydrolysis rate of the acetal group and found a direct correlation. Additional encapsulation studies with doxorubicin (DOX) revealed that surface potential and charge density represent additional key factors not only for the loading capacity, but also for the release profile of the nanogels. The option to tune such properties simply by the addition of a co-factor, in this case, the carboxylate-pillar[5]arenes provides a powerful tool to optimize characteristics of functional nanogels for drug delivery or other applications.