Photothermal Fenton Nanocatalysts for Synergetic Cancer Therapy in the Second Near-Infrared Window

Abstract

Chemodynamic therapy (CDT) that utilizes endogenous hydrogen peroxide (H2O2) to produce reactive oxygen species (ROS) to kill cancer cells has shown a promising strategy for malignant tumor treatment. Nevertheless, limited H2O2 levels in the tumor microenvironment often compromise the therapeutic benefits of CDT, leading to cancer recurrence and metastasis. Herein, a second near-infrared (NIR-II) photothermal Fenton nanocatalyst (PFN) was developed for activatable magnetic resonance imaging (MRI)-guided synergetic photothermal therapy (PTT) and CDT of pancreatic carcinoma. Such a PFN consists of manganese dioxide (MnO2), copper sulfide (CuS), and human serum albumin (HSA), which serve as the activatable imaging contrast agent, the NIR-II photothermal agent and Fenton catalyst, and the stabilizer, respectively. The acidic tumor microenvironment increased the relaxivity of PFN by 2.1-fold, allowing for improved imaging performance and monitoring of nanoparticle accumulation in tumors. Under NIR-II laser irradiation at 1064 nm, PFN generates local heat, which not only permits PTT but also enhances the nanocatalyst-mediated Fenton-like reaction. As such, PFN exerts a synergetic action to completely ablate xenografted tumor models in living animals, while the sole CDT fails to do so. This study thus provides an NIR-II photothermal nanocatalyst for potential treatment of deep-seated tumors.

Emerging Nanomedicine‐Enabled/Enhanced Nanodynamic Therapies beyond Traditional Photodynamics

“…The reaction rate and degree of Fenton reaction for CDT are influenced by the reaction conditions. [152][153][154] Especially, the local temperature elevation can expedite the Fenton reaction rate and enhance the reaction degree for ROS production. [155][156][157][158][159] On this ground, we recently designed photothermal-enhanced Fenton composite nanocatalysts for synergistic PTT and CDT against tumor, which were based on Fe 3 O 4 /GOD-functionalized polypyrrole (PPy) nanoparticles (Figure 11b).…”

Photosensitizer Nanoparticles Boost Photodynamic Therapy for Pancreatic Cancer Treatment

“…The therapeutic mechanism of CDT lies in the catalysis of metal ions-based nanoparticles to convert endogenous H 2 O 2 into cytotoxic hydroxyl radicals ( · OH) via Fenton-like reaction [ 39 ]. Although CDT is an unremitting chemical process overcoming the limitations of light attenuation and hypoxic TME [ 75 ], the efficacy of CDT is always restricted by the unsatisfactory catalytic efficiency of currently developed metal-based nanocatalysts [ 39 ]. The extent of acidity in TME also restricts the activity of these metallic catalysts, which obviously decreases CDT performance [ 76 ].…”

Photodynamic Therapy for Pancreatic Ductal Adenocarcinoma

“…Due to the relatively low tissue attenuation coefficient of ultrasound, it can penetrate deeply into the tissue [114]. Yet another ROS-dependent strategy is chemodynamic therapy (CDT), which works based on H 2 O 2 conversion into toxic hydroxyl radicals (OH) and leads to cell apoptosis [115]. Combination of PDT and SDT or CDT are relatively new approaches that can overcome the hypoxia in PDAC and as a result enhance the generation of ROS in pancreatic cancer [116][117][118].…”