A tumor microenvironment responsive nanosystem for chemodynamic/chemical synergistic theranostics of colorectal cancer

Theranostics. 2021 Aug 18;11(18):8909-8925. doi: 10.7150/thno.61651. eCollection 2021.

Abstract

Rationale: The synergism of new modalities alongside chemodynamic therapy into common chemotherapy has shown promising potential in clinical applications. This paper reports a tumor microenvironment-responsive nanosystem for chemodynamic/chemical synergistic therapy and magnetic resonance imaging (MRI). Methods: The biodegradable nanosystem is synthesized using a surface-modified chain transfer agent for surface-initiated living radical polymerization of the chemotherapeutic drug. Results: In this nanosystem, named CAMNSN@PSN38, the cycling time and solubility of the chemotherapeutic drug are improved. The nanoparticles delivered to tumor tissues gradually release the chemotherapeutic drug and Mn2+ through glutathione (GSH)-triggered biodegradation in the tumor microenvironment. SN38, the released chemotherapeutic drug, not only shows excellent chemical therapy effects but also improves the generation of H2O2. Furthermore, with the Fenton-like agent Mn2+, the generation of reactive oxygen species (ROS) is improved markedly. Finally, CAMNSN@PSN38 shows excellent inhibition of tumor growth in three colorectal cancer tumor models, with an improved accumulation of ROS and controlled release of SN38. Conclusions: The CAMNSN@PSN38-mediated chemodynamic/chemical synergistic therapy provides a promising paradigm for the treatment and MRI-guided therapy of colorectal cancer.

Keywords: Chemodynamic therapy; Magnetic resonance imaging; Microenvironment-responsive; Nanotheranostics; Synergistic therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • China
  • Colorectal Neoplasms / drug therapy
  • Drug Delivery Systems / methods*
  • Drug Liberation
  • Drug Synergism
  • Female
  • Hydrogen Peroxide / pharmacology
  • Magnetic Resonance Imaging / methods
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticle Drug Delivery System / pharmacology*
  • Nanoparticles / administration & dosage
  • Neoplasms / drug therapy
  • Precision Medicine / methods
  • Reactive Oxygen Species / metabolism
  • Theranostic Nanomedicine
  • Tumor Microenvironment / drug effects*
  • Xenograft Model Antitumor Assays

Substances

  • Nanoparticle Drug Delivery System
  • Reactive Oxygen Species
  • Hydrogen Peroxide