Multifunctional nanomedicines-enabled chemodynamic-synergized multimodal tumor therapy via Fenton and Fenton-like reactions

Abstract

Chemodynamic therapy (CDT) is well-known for using the tumor microenvironment to activate the Fenton reaction or Fenton-like reaction to generate strong oxidative hydroxyl radicals for tumor-specific treatment. It is highly selective and safe, without depth limitation of tissue penetration, and shows its potential as a new green therapeutic method with great clinical application. However, the catalytic efficiency of reagents involved in the Fenton reaction is severely affected by the inherent microenvironmental limitations of tumors and the strict Fenton reaction-dependent conditions. With the increasing application of nanotechnology in the medical field, combined therapies based on different types of functional nanomaterials have opened up new avenues for the development of next-generation CDT-enhanced system. This review will comprehensively exemplify representative results of combined therapies of CDT with other antitumor therapies such as chemotherapy, phototherapy, sonodynamic therapy, radiation therapy, magnetic hyperthermia therapy, immunotherapy, starvation therapy, gas therapy, gene therapy, oncosis therapy, or a combination thereof for improving antitumor efficiency from hundreds of the latest literature, introduce strategies such as the ingenious design of nanomedicines and tumor microenvironment regulations to enhance the combination therapy, and further summarize the challenges and future perspective of CDT-based multimodal anticancer therapy.

Nanomedicine as a multimodal therapeutic paradigm against cancer: on the way forward in advancing precision therapy

“…22 Recently, Gao et al meti-culously reviewed the potential of combining nanomedicines with radiotherapy, chemotherapy, immunotherapy, phototherapy, etc., in various cancers to improve the treatment efficacy. 23…”

Advances in Nanodelivery Systems Based on Metabolism Reprogramming Strategies for Enhanced Tumor Therapy

“…Consequently, this must be taken into account when treating tumors. Nanodelivery systems are well-used in metabolism reprogramming strategies due to their excellent drug loading, target modification, and ability to protect enzyme activity. − The metabolite of lactic acid, H 2 O 2 , could in turn react with many metal ions, such as Fe 2+ , Cu 2+ , and Zn 2+ , to generate oxidative hydroxyl radicals for tumor treatment. , These metal ion compounds could be easily processed to obtain many types of nanodelivery systems. , This built a bridge between nanodelivery systems and metabolism reprogramming strategies. Unexpectedly, tumors improve their resistance to oxidative stress by enhancing their own lipid metabolism , and amino acid metabolism, e.g., glutamine metabolism, glutathione (GSH) metabolism, etc. , These issues in turn need to be addressed by nanodelivery systems based on tumor metabolism reprogramming strategies.…”

“…20−22 The metabolite of lactic acid, H 2 O 2 , could in turn react with many metal ions, such as Fe 2+ , Cu 2+ , and Zn 2+ , to generate oxidative hydroxyl radicals for tumor treatment. 23,24 These metal ion compounds could be easily processed to obtain many types of nanodelivery systems. 25,26 This built a bridge between nanodelivery systems and metabolism reprogramming strategies.…”

Intelligent Nanoplatform Integrating Macrophage and Cancer Cell Membrane for Synergistic Chemodynamic/Immunotherapy/Photothermal Therapy of Breast Cancer

“…CDT employs Fenton catalysts to convert the overexpressed hydrogen peroxide (H 2 O 2 ) in tumors into highly cytotoxic hydroxyl radicals ( • OH), effectively inhibiting tumor growth. − Additionally, CDT induces immunogenic cell death, leading to the release of tumor-associated antigens. However, the effectiveness of T cell activation is hindered by the suboptimal antigen uptake and presentation by dendritic cells (DCs) within the tumor’s immunosuppressive microenvironment. , Therefore, it is crucial to design a CDT agent that can enhance the T cell activation efficiency and prolong the circulation time.…”

“…However, the effectiveness of T cell activation is hindered by the suboptimal antigen uptake and presentation by dendritic cells (DCs) within the tumor's immunosuppressive micro- environment. 15,16 Therefore, it is crucial to design a CDT agent that can enhance the T cell activation efficiency and prolong the circulation time.…”