Functional Self-Immolative Hydrogels with Dendritic Cross-Linkers for Controlled Drug Delivery

In the biomedical field, the design of materials with controlled degradation is highly desired. Herein, we present a family of dendritic hydrogels accomplished through copper-assisted azide-alkyne cycloaddition click reaction between dendritic cross-linkers and complementary linear polymers. As cross-linkers, an innovative family of bifunctional carbosilane dendrimers was designed for this purpose, bearing multiple alkyne groups available for network formation as well as pendant hydroxyl groups for postfunctionalization. Additionally, different azide-pendant polymers were employed, including difunctional poly-(ethylene glycol) with cleavable and noncleavable nature, as well as poly-(ethyl glyoxylate) with and without self-immolative behavior. The rational design of the dendritic hydrogels, through the careful selection of these two components, enabled an accurate manipulation of properties like swelling and mechanical properties. The network degradation could be tuned from a few hours, for a traditional ester-cleavable dendritic hydrogel, to several days under pH-controlled conditions, for the self-immolative hydrogel (SIH). The impact of network degradation on the release of curcumin as a model drug was also confirmed. This work showcased the potential of dendritic SIHs for biomedical applications.