Traditional tumor treatments, including chemotherapy, radiotherapy, photodynamic therapy, and photothermal therapy, have been developed and used to treat different types of cancer. Recently, chemodynamic therapy (CDT) has been emerged as a novel cancer therapeutic strategy. CDT utilizes Fenton or Fenton-like reaction to generate highly cytotoxic hydroxyl radicals (·OH) from endogenous hydrogen peroxide (H2 O2 ) to kill cancer cells, which displays promising therapeutic potentials for tumor treatment. However, the low catalytic efficiency and off-target side effects of Fenton reaction limit the biomedical application of CDT. In this regard, various strategies have been implemented to potentiate CDT against tumor, including retrofitting the tumor microenvironment (e.g., increasing H2 O2 level, decreasing reductive substances, and reducing pH), enhancing the catalytic efficiency of nanocatalysts, and other strategies. This review aims to summarize the development of CDT and summarize these recent progresses of nanocatalyst-mediated CDT for antitumor application. The future development trend and challenges of CDT are also discussed. This article is protected by copyright. All rights reserved.

Nanocatalyst-Mediated Chemodynamic Tumor Therapy.

The convenience of injectable hydrogels that can provide high loading of diverse phototherapy agents and further long-time retention at the tumor site has attracted tremendous interest in simultaneous photothermal and photodynamic cancer therapies. However, to incorporate the phototherapy agents into hydrogels, complex modifications are generally unavoidable. Moreover, these phototherapy agents usually suffer from low efficiency and work at different irradiation wavelengths outside the near infrared windows. Hence, a method for the fabrication of an injectable hydrogel for simultaneous photothermal therapy and photodynamic therapy, through the Schiff-base reaction between amido modified carbon dots (NCDs) and aldehyde modified cellulose nanocrystals is proposed. The NCDs act as both phototherapy agents and crosslinkers to form hydrogels. Significantly, the NCDs demonstrate an extremely high photothermal conversion efficiency of 77.6% which is among the highest levels for photothermal agents and a high singlet quantum yield of 0.37 under a single 660 nm light-emitting diode irradiation. The hydrogels are examined through in vitro and in vivo animal experiments which show nontoxic and effectively tumor inhibition. Thus, the strategy of direct reaction of phototherapy agents and the matrix not only provides new strategies for injectable hydrogel fabrication but paves a new road for advanced tumor treatment.

An Injectable Hydrogel for Simultaneous Photothermal Therapy and Photodynamic Therapy with Ultrahigh Efficiency Based on Carbon Dots and Modified Cellulose Nanocrystals

Engineered gold/black phosphorus nanoplatforms with remodeling tumor microenvironment for sonoactivated catalytic tumor theranostics

Nanozyme‐based tumor catalytic therapy has attracted widespread attention in recent years, but its therapeutic outcome is drastically diminished by species of nanozyme, concentration of substrate, pH value, and reaction temperature, etc. Herein, a novel Cu‐doped polypyrrole nanozyme (CuP) with trienzyme‐like activities, including catalase (CAT), glutathione peroxidase (GPx), and peroxidase (POD), is first proposed by a straightforward one‐step procedure, which can specifically promote O2 and ·OH elevation but glutathione (GSH) reduction in tumor microenvironment (TME), causing irreversible oxidative stress damage to tumor cells and reversing the redox balance. The PEGylated CuP nanozyme (CuPP) has been demonstrated to efficiently reverse immunosuppressive TME by overcoming tumor hypoxia and re‐educating macrophage from pro‐tumoral M2 to anti‐tumoral M1 phenotype. More importantly, CuPP exhibits hyperthermia‐enhanced enzyme‐mimic catalytic and immunoregulatory activities, which results in intense immune responses and almost complete tumor inhibition by further combining with αPD‐L1. This work opens intriguing perspectives not only in enzyme‐catalytic nanomedicine but also in macrophage‐based tumor immunotherapy.

Chen Ting

Papers

Engineered gold/black phosphorus nanoplatforms with remodeling tumor microenvironment for sonoactivated catalytic tumor theranostics

Renal-Clearable Ultrasmall Polypyrrole Nanoparticles with Size-Regulated Property for Second Near-Infrared Light-Mediated Photothermal Therapy