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

 

作者： Jia Zhou, Tianliang Li, Yiran Zhang, Xiaoyu Xu, Chunlei Zhang, Yuehua Li, Daxiang Cui, Yingsheng Cheng

Department of Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233 China

 

摘要：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 r1 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 Gd3+. 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 r1 value of 26.391 s−1 mm−1, which is about 5.5‐fold larger than Gd‐DTPA (≈4.8 s−1 mm−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.