Construction of pH-Sensitive Dynamic Composite Hydrogels and Their Local Targeted Antitumor Research

The treatment of solid tumors is often limited by traditional methods such as surgery and chemotherapy. These methods potentially kill cancer cells but cause significant systemic toxicity and tissue damage. This research introduces a pH-responsive injectable hydrogel (named as Gel-FOEDS) containing fluorinated ortho-ester-loaded dasatinib (DAS) and sunitinib (SUN) and provides a potential strategy to overcome certain limitations of traditional therapies. This gel acts as a "drug pool" that delivers, penetrates, and retains drugs-enabling sustained, deep tumor delivery. Studies have shown that FOE can carry DAS and SUN to escape from the hydrogel rapidly and penetrate deep into the tissue. The imine bond's acid instability in the hydrogel and FOE's specific response to the acidic microenvironment work together for targeted, controllable release of DAS and SUN at the tumor site. The self-assembly of DAS and SUN forms nanoparticles (NPs), which prolongs their retention in tumor tissues. In the mouse solid tumor model, the Gel-FOEDS group demonstrated the strongest antitumor activity, with some tumor-bearing mice achieving complete tumor regression. Our results indicate this composite hydrogel provides an efficient local delivery solution for tyrosine kinase inhibitors (TKIs) and offers a low-side-effect strategy for the treatment of solid tumors.