Enhanced imaging techniques using contrast agents enable high-resolution structural imaging to reveal space-occupying lesions but rarely provide detailed molecular information. To this end, we report a structural and molecular fusion magnetic resonance imaging (MRI) nanoprobe for differential diagnosis between benign and malignant tumors. This fusion nanoprobe, termed FFT NPs, follows a working mechanism involving a T1-/T2-weighted magnetic resonance tuning effect (MRET) between a magnetic Fe3O4 core and a paramagnetic Fe-tannic acid (Fe-TA) shell. The FFT NPs with an “always-on” inert T2 signal provide structural MRI (sMRI) contrast of tumors while affording an activated T1 signal in the presence of ATP, which is overproduced during the rapid growth of malignant tumors to enable molecular MRI (mMRI) of tumor lesions. We propose the use of the ratiometric mMRI:sMRI intensity to assist in the differential diagnosis of malignant 4T1 tumors from benign L929 fibroblast tumors. Furthermore, the dissociated FFT NPs were found to be able to catalyze H2O2 conversion in 4T1 tumors to generate excess reactive oxygen species (ROS) for chemodynamic therapy. The described fusion nanoprobe strategy enables the differential diagnosis of tumors from a combined spatial and molecular perspective with one-stop MRI imaging with potential applications in precision intervention.
Qinghua Xie,Xuemei Wang,Gaorui Zhang,Dawei Zhou,Yuxuan Zhao,Hong Liu,Jiazhi Duan,Dexin Yu,Yuanhua Sang
Individual theranostic agents with dual-mode MRI responses and therapeutic efficacy have attracted extensive interest due to the real-time monitor and high effective treatment, which endow the providential treatment and avoid the repeated medication with side effects. However, it is difficult to achieve the integrated strategy of MRI and therapeutic drug due to complicated synthesis route, low efficiency and potential biosafety issues. In this study, novel self-assembled ultrasmall Fe 3 O 4 nanoclusters were developed for tumor-targeted dual-mode T 1 /T 2 -weighted magnetic resonance imaging (MRI) guided synergetic chemodynamic therapy (CDT) and chemotherapy. The self-assembled ultrasmall Fe 3 O 4 nanoclusters synthesized by facilely modifying ultrasmall Fe 3 O 4 nanoparticles with 2,3-dimercaptosuccinic acid (DMSA) molecule possess long-term stability and mass production ability. The proposed ultrasmall Fe 3 O 4 nanoclusters shows excellent dual-mode T 1 and T 2 MRI capacities as well as favorable CDT ability due to the appropriate size effect and the abundant Fe ion on the surface of ultrasmall Fe 3 O 4 nanoclusters. After conjugation with the tumor targeting ligand Arg-Gly-Asp (RGD) and chemotherapy drug doxorubicin (Dox), the functionalized Fe 3 O 4 nanoclusters achieve enhanced tumor accumulation and retention effects and synergetic CDT and chemotherapy function, which serve as a powerful integrated theranostic platform for cancer treatment.