A Light‐Responsive Injectable Hydrogel with Remodeling Tumor Microenvironment for Light‐Activated Chemodynamic Therapy

Abstract

Chemodynamic therapy (CDT) based on Fenton-like reaction is often limited by the tumor microenvironment (TME), which has insufficient hydrogen peroxide, and single CDT treatment is often less efficacious. To overcome these limitations, a hydrogel-based system is designed to enhance the redox stress (EOH) by loading the composite nanomaterial Cu-Hemin-Au, into the agarose hydrogels. The hydrogels can reach the tumor site upon intratumoral injection, and then coagulate and stay for extended period. Once irradiated with near-infrared light, the Cu-Hemin-Au act as a photothermal agent to convert the light energy into heat, and the EOH gradually heated up and softened, releasing the Cu-Hemin-Au residing in it to achieve photothermal therapy (PTT). Benefiting from the glucose oxidase (GOx)-like activity of the Au nanoparticles, glucose in the tumor cells is largely consumed, and hydrogen peroxide (H 2 O 2 ) is generated in situ, and then Cu-Hemin-Au react with sufficient H 2 O 2 to generate a large amount of reactive oxygen species, which promote the complete inhibition of tumor growth in mice during the treatment cycle. The hydrogel system for the synergistic enhancement of oxidative stress achieves good PTT/CDT synergy, providing a novel inspiration for the next generation of hydrogels for application in antitumor therapy.

The progress of research on the application of redox nanomaterials in disease therapy

“…The flexibility and softness of nanogels allow increased sensitivity to different stimuli and easier penetration into tissues ( Ding et al, 2018 ; Mohtashamian et al, 2018 ). Redox-active units, such as disulfide, ditellurium, and diselenide bonds ( Kumar et al, 2019 ), are attached to the network or in-between drugs and combined using other inorganic redox nanoparticles with nanogels to construct redox nanogel platforms, which have emerged as promising candidates as efficient redox-responsive drug delivery systems ( Yin et al, 2020 ; Huang et al, 2021a ; Zhu et al, 2021 ; Liu et al, 2023 ).…”

CeO2 and Glucose Oxidase Co-Enriched Ti3C2Tx MXene for Hyperthermia-Augmented Nanocatalytic Cancer Therapy

“…Cancer cells cultivate a unique tumor microenvironment (TME) marked by pronounced acidity and hypoxia, stemming from their increased metabolic needs and an acute dependency on the steady influx of glucose to foster rapid growth. − The progression of nanomedicine has opened up new opportunities for cancer treatment, with nanocatalytic therapy assuming a prominent position. , This approach primarily involves a chemical reaction in situ within the tumor, employing catalytically active nanomaterials to produce toxic substances for targeting and eliminating tumor cells. To effectively leverage these TME attributes, considerable research endeavors have focused on the advancement of efficacious and low-toxicity nanocatalytic treatments leveraging TME characteristics. − However, the intrinsic hypoxic conditions within the tumors substantially limit the effectiveness of photodynamic therapy (PDT), thereby fortifying tumor proliferation and metastasis. − Notwithstanding numerous attempts such as deploying nanoparticles bearing catalase (CAT)-like activity to transmute hydrogen peroxide (H 2 O 2 ) into oxygen (O 2 ) to neutralize tumor cell hypoxia, the outcomes have been suboptimal due to the scant endogenous H 2 O 2 availability within tumors. − Concomitantly, endogenous H 2 O 2 proves insufficient for sustained reactive oxygen species (ROS) production. − As a result, the development of a chemical reaction in situ system, custom-tailored to a TME, is critically essential for establishing a robust platform to regulate the levels of H 2 O 2 , O 2 , and glucose, ultimately contributing to the inhibition of tumor cell proliferation.…”