ABC triblock bottlebrush copolymer-based injectable hydrogels: design, synthesis, and application to expanding the therapeutic index of cancer immunochemotherapy

. Specifically, intratumoral administration of TBCs containing paclitaxel and resiquimod-the latter a potent Toll-like receptor (TLR) 7/8 agonist-into mice bearing subcutaneous CT26 tumors resulted in a significantly enhanced therapeutic index compared to the administration of these two drugs alone. This effect is attributed to the TBC hydrogel maintaining a high local drug concentration, thus reducing systemic immune activation and local inflammation. Collectively, this work represents, to our knowledge, the first example of thermally-responsive TBCs designed for multi-compartment hydrogel formation, establishing these materials as versatile scaffolds for self-assembly and drug delivery.