Journal
THERANOSTICS
Volume 11, Issue 18, Pages 8909-8925Publisher
IVYSPRING INT PUBL
DOI: 10.7150/thno.61651
Keywords
Chemodynamic therapy; Nanotheranostics; Microenvironment-responsive; Magnetic resonance imaging; Synergistic therapy
Categories
Funding
- National Natural Science Foundation of China [81871403]
- Key Research and Development Program of Zhejiang Province [2019C03014]
- China Postdoctoral Science Foundation [2020M671716]
- Fundamental Research Funds for the Central Universities
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This study presents a tumor microenvironment-responsive nanosystem for chemodynamic/chemical synergistic therapy and magnetic resonance imaging. The nanosystem improves the cycling time and solubility of chemotherapeutic drugs, releasing them gradually in tumor tissues through glutathione-triggered biodegradation. With improved generation of reactive oxygen species and controlled release of the chemotherapeutic drug, it shows excellent inhibition of tumor growth in colorectal cancer models.
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.
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