Currently, cancer is the second largest cause of death worldwide and has reached critical levels. In spite of all the efforts, common treatments including chemotherapy, photodynamic therapy, and photothermal therapy suffer from various problems which limit their efficiency and performance. For this reason, different strategies are being explored which improve the efficiency of these traditional therapeutic methods or treat the tumor cells directly. One such strategy utilizing the Fenton reaction has been investigated by many groups for the possible treatment of cancer cells. This approach is based on the knowledge that high levels of hydrogen peroxide exist within cancer cells and can be used to catalyze the Fenton reaction, leading to cancer-killing reactive oxygen species. Analysis of the current literature has shown that, due to the diverse morphologies, different sizes, various chemical properties, and the tunable structure of nanoparticles, nanotechnology offers the most promising method to facilitate the Fenton reaction with cancer therapy. This review aims to highlight the use of the Fenton reaction using different nanoparticles to improve traditional cancer therapies and the emerging Fenton-based therapy, highlighting the obstacles, challenges, and promising developments in each of these areas.

Cancer Treatment through Nanoparticle-Facilitated Fenton Reaction

Metal-organic frameworks: A novel platform for combined advanced therapies

Chemodynamic therapy (CDT), a novel cancer therapeutic strategy defined as the treatment using Fenton or Fenton-like reaction to produce •OH in the tumor region, was first proposed by Bu, Shi, and co-workers in 2016. Recently, with the rapid development of Fenton and Fenton-like nanomaterials, CDT has attracted tremendous attention because of its unique advantages: 1) It is tumor-selective with low side effects; 2) the CDT process does not depend on external field stimulation; 3) it can modulate the hypoxic and immunosuppressive tumor microenvironment; 4) the treatment cost of CDT is low. In addition to the Fe-involved CDT strategies, the Fenton-like reaction-mediated CDT strategies have also been proposed, which are based on many other metal elements including copper, manganese, cobalt, titanium, vanadium, palladium, silver, molybdenum, ruthenium, tungsten, cerium, and zinc. Moreover, CDT has been combined with other therapies like chemotherapy, radiotherapy, phototherapy, sonodynamic therapy, and immunotherapy for achieving enhanced anticancer effects. Besides, there have also been studies that extend the application of CDT to the antibacterial field. This review introduces the latest advancements in the nanomaterials-involved CDT from 2018 to the present and proposes the current limitations as well as future research directions in the related field.

Chemodynamic Therapy via Fenton and Fenton-Like Nanomaterials: Strategies and Recent Advances.

Recent advances in enhanced chemodynamic therapy strategies

Nanomaterial-induced ferroptosis for cancer specific therapy

Metal-organic frameworks join hands to create an anti-cancer nanoplatform based on 808 nm light driving up-conversion nanoparticles

Construction of thiol-capped ultrasmall Au-Bi bimetallic nanoparticles for X-ray CT imaging and enhanced antitumor therapy efficiency.

Photodynamic therapy (PDT) is a light-based modality for tumor treatment that involves the generation of reactive oxygen species (ROS) by the combination of light, a photosensitizer, and molecular oxygen. Nevertheless, the therapeutic effects of PDT are limited by hypoxic conditions that worsen with oxygen consumption during the PDT process. Photo/chemodynamic therapy (PCDT) based on the Fenton reaction is one strategy to improve ROS generation, provided a highly effective Fenton reagent is developed. In this research, SiO2@Cu7S4 nanotubes (NTs) were synthesized as a PCDT agent. This double-valence metal-sulfide composite material can react with H2O2 at the tumor site. SiO2@Cu7S4 NTs can produce more ROS than the traditional PDT agents, and besides, they can also be used as a photothermal therapy (PTT) agent. SiO2@Cu7S4 NTs will trigger the PTT effect under 808 nm irradiation and generate a large amount of heat to eradicate cancer cells. This heat will also promote the PCDT effect by increasing the reaction rate. Thus, the SiO2@Cu7S4 NT is a suitable material for PCDT and PTT synergistic oncotherapy. The 808 nm laser is selected as the appropriate excitation source, providing adequate penetration and minimal harm to normal cells. The experimental data presented herein demonstrate the promising photosensitive, Fenton-like, and photothermal performance of SiO2@Cu7S4 NTs. Furthermore, the findings could promote the development of PCDT and PTT synergistic therapy. Thus, this research provides a feasible method to design a single, multifunctional material for cancer treatment.

SiO2@Cu7S4 nanotubes for photo/chemodynamic and photo-thermal dual-mode synergistic therapy under 808 nm laser irradiation

Near infrared (NIR) light detonated phototherapy for cancer treatment based on photothermal therapy (PTT) and photodynamic therapy (PDT) has attracted increasing attention owing to its deep tissue penetration. However, the low absorption ability and therapeutic efficiency of the photosensitive drug have restricted the development of phototherapy to a great degree. Herein, a kind of IR808 dye sensitized glutathione (GSH) cladded Au-Bi bimetallic nanoparticles (Au-Bi-GSH@IR808) was prepared to enhance the inhibition effect of tumors. In this nanoplatform, the construction of GSH cladded Au-Bi bimetallic nanoparticles can effectively generate 1O2 while exhibiting outstanding photothermal conversion efficiency (η = 34.2%) upon 808 nm laser irradiation. Furthermore, IR808 as a small molecule dye endows the Au-Bi-GSH@IR808 with a higher 808 nm light absorption ability and stronger photothermal and photodynamic effects. The IR808 sensitized Au-Bi bimetallic nanoparticles with a small size (5 nm), hydrophilia and dispersible nature, exhibit a noticeably enhanced therapeutic peculiarity. Additionally, the prominent CT imaging property of Au-Bi-GSH@IR808 means it is expected to be used as a CT imaging contrast agent in clinical applications. The results of the in vitro and in vivo experiments indicate that the synthesized nanoparticles have an excellent ablation effect on cancer cells, and they are expected to be widely used in the accurate diagnosis and treatment of cancer.

Hongjiao Ji

Papers

Metal-organic frameworks join hands to create an anti-cancer nanoplatform based on 808 nm light driving up-conversion nanoparticles

Construction of thiol-capped ultrasmall Au-Bi bimetallic nanoparticles for X-ray CT imaging and enhanced antitumor therapy efficiency.

SiO2@Cu7S4 nanotubes for photo/chemodynamic and photo-thermal dual-mode synergistic therapy under 808 nm laser irradiation

Integration of IR-808 and thiol-capped Au-Bi bimetallic nanoparticles for NIR light mediated photothermal/photodynamic therapy and imaging.