Multifunctional Drug Delivery Nanoparticles Based on Fe-Containing Metal–Organic Framework for Fluorescence Image-Guided Combined Chemical/Chemodynamic/Photodynamic Colorectal Cancer Treatment

Nanoagents with multiple functions, including fluorescence imaging, photodynamic and chemodynamic properties, and drug delivery capabilities, have great advantages for the synergistic treatment of cancer. However, designing and creating such nanoagents is challenging. Herein, we report a nanocomposite (denoted CPT@MIL(Fe)-TCPP, C@M(Fe)T) based on the MIL-101(Fe)-NH₂ framework, which is obtained by loading CPT via electrostatic attraction and modifying TCPP onto MIL-101(Fe)-NH₂ through amidation reaction. C@M(Fe)T contains abundant Fe³⁺, which can undergo a Fenton reaction in the tumor microenvironment rich in GSH and H₂O₂ to generate hydroxyl radicals and induce oxidative stress. Meanwhile, CPT, when carried by nanomaterials, can effectively accumulate at the tumor site by the EPR effect of nanomaterials to enable chemotherapy. TCPP modified on the surface of the nanomaterial, due to its photosensitive property, can efficiently generate singlet oxygen and realize fluorescence imaging of the cancer location. Both cell assay and animal test show that C@M(Fe)T exhibits a good inhibitory effect on HCT116 colon cancer cells, while avoiding serious injury to other significant organs of the body. Moreover, after the mice were injected with C@M(Fe)T, obvious fluorescent signals were generated at the tumor sites. Overall, the C@M(Fe)T nanocomposite presents a promising strategy for cancer treatment by enabling fluorescence image-guided trimodal CT/CDT/PDT of colorectal cancer and integrating diagnosis and treatment.