Metal–Drug–Protein Assemblies: Gd3+ Self-Enhanced Magnetic Resonance Imaging, High-Sensitive Tumor-Targeting Imaging and Efficient Chemo-Phototherapy

Magnetic resonance imaging (MRI) contrast agents are broadly employed for better clinical trials in MR imaging. Magnevist solution (Gd-DTPA), a clinical MRI contrast agent, possesses inherent shortcomings like poor r 1 relaxation, short half-time, nephrotoxicity, etc. To overcome these problems, Gd-DTPA-grafted protein assemblies (Gd-P-ABs) loading with anticancer drug cisplatin and photosentizer IR-780 are constructed via chelation of Gd 3+ . Gd-P-ABs exhibit dual MR/fluorescence (FL) imaging–guided chemo/photothermal therapy. Interestingly, Gd-P-ABs behave as aggregation-enhanced magnetic resonance imaging with an extremely high r 1 value of 26.391 s −1 m m −1 , which is about 5.5-fold larger than Gd-DTPA (≈4.8 s −1 m m −1 ). Consequently, better MRI performance is presented with the same concentration of Gd ions. When exposed to acidic tumor microenvironment and light irradiation, Gd-P-ABs show significant drug release capacity. Good cell killing ability in vitro is also determined due to effective folate-targeting ability and high photo–heat conversion. In vivo MR/FL imaging results reveal that Gd-P-ABs possess high-sensitivity tumor-targeting imaging and long tumor retention, which are attributed to the folate-targeting ability and small size effect. Combined chemo/photothermal therapy in vivo demonstrates that the tumor can be eventually ablated. Altogether, the Gd-P-ABs possess great potential for clinical imaging-guided tumor therapy.