Hydroxyl radical (•OH)-mediated chemodynamic
therapy (CDT) is an emerging antitumor strategy, however,
acid deficiency in the tumor microenvironment (TME) hampers its efficacy. In this study, a new
injectable hydrogel was developed as an
acid-enhanced CDT system (AES) for improving
tumor therapy. The AES contains
iron-
gallic acid nanoparticles (FeGA) and α-cyano-4-hydroxycinnamic
acid (α-CHCA). FeGA converts near-infrared
laser into heat, which results in
agarose degradation and consequent α-CHCA release. Then, as a monocarboxylic
acid transporter inhibitor, α-CHCA can raise the acidity in TME, thus contributing to an increase in ·OH-production in FeGA-based CDT. This approach was found effective for killing
tumor cells both in vitro and in vivo, demonstrating good therapeutic efficacy. In vivo investigations also revealed that AES had outstanding biocompatibility and stability. This is the first study to improve FeGA-based CDT by increasing intracellular acidity. The AES system developed here opens new opportunities for effective
tumor treatment.