An Injectable Hydrogel for Enhanced FeGA-Based Chemodynamic Therapy by Increasing Intracellular Acidity

Abstract

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.

Construction of SLC16A1/3 Targeted Gallic Acid-Iron-Embelin Nanoparticles for Regulating Glycolysis and Redox Pathways in Cervical Cancer

“…Different concentrations of GA-Fe solutions (0, 0.25, 0.50, 0.75, and 1.00 mg•mL −1 ) were placed in the centrifuge tube to test the photothermal properties of GA-Fe nanoparticles. Then they were irradiated with an 808 nm laser for 10 min with 1.0 and 2.0 W•cm −2 laser, and the temperature values were obtained every 10 s. 19 2.2.9. Intracellular Endocytosis Analysis.…”

“…17,18 The photothermal effect of GA-Fe nanoparticles and the reducibility of GA in an acidic environment promote the catalytic activity and continuous supply of Fe 2+ , further driving the Fenton reaction and promoting ROS accumulation. 19 In addition, the accumulation of lactic acid by EMB-targeted SLC16A1/3 enhanced the oxidative stress effects of GA-Fe nanoparticles.…”

“…GA and related polyphenol compounds can promote the uptake of nanoparticles by cancer cells, and nanoparticles coated with polyphenolic compounds have been employed to design drug delivery systems for the treatment of solid tumors . It has been reported that GA coordinates with iron ion (Fe 3+ ) to form stable organometallic complex GA-Fe, which can deliver drugs and be used as a highly catalytically active chemokinetic therapy agent based on Fe 3+ /Fe 2+ conversion and photothermal therapy (PTT). , The photothermal effect of GA-Fe nanoparticles and the reducibility of GA in an acidic environment promote the catalytic activity and continuous supply of Fe 2+ , further driving the Fenton reaction and promoting ROS accumulation . In addition, the accumulation of lactic acid by EMB-targeted SLC16A1/3 enhanced the oxidative stress effects of GA-Fe nanoparticles.…”

Application of Hydrogels as Carrier in Tumor Therapy: A Review

“…However, chemotherapy has significant limitations due to systemic distribution [45] . In contrast, CDT is a specific treatment for tumor [61] . CDT consumes endogenous H 2 O 2 through Fenton or Fenton‐like reactions to generate cytotoxic ROS, especially hydroxyl radicals, which can inhibit cell growth and kill tumor cells [62] .…”

“…[45] In contrast, CDT is a specific treatment for tumor. [61] CDT consumes endogenous H 2 O 2 through Fenton or Fenton-like reactions to generate cytotoxic ROS, especially hydroxyl radicals, which can inhibit cell growth and kill tumor cells. [62] Wang first developed a catechol-crosslinked hyaluronic acid hydrogel loaded with copper sulfate.…”