Renal-Clearable Ultrasmall Coordination Polymer Nanodots for Chelator-Free 64Cu-Labeling and Imaging-Guided Enhanced Radiotherapy of Cancer
Sida Shen,† Dawei Jiang,‡,§ Liang Cheng,*,† Yu Chao,† Kaiqi Nie,† Ziliang Dong,† Christopher J. Kutyreff,‡ Jonathan W. Engle,‡ Peng Huang,§ Weibo Cai,*,‡ and Zhuang Liu*,†
†Institute of Functional Nano and Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou, Jiangsu 215123, China
‡Departments of Radiology and Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin 53705, United States
§Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen 518060, China
Developing tumor-homing nanoparticles with integrated diagnostic and therapeutic functions, and meanwhile could be rapidly excreted from the body, would be of great interest to realize imagingguided precision treatment of cancer. In this study, an ultrasmall coordination polymer nanodot (CPN) based on the coordination between tungsten ions (WVI) and gallic acid (W-GA) was developed via a simple method. After polyethylene glycol (PEG) modification, PEGylated W-GA (W-GA-PEG) CPNs with an ultrasmall hydrodynamic diameter of 5 nm were rather stable in various physiological solutions. Without the need of chelator molecules, W-GA-PEG CPNs could be efficiently labeled with radioisotope 64Cu2+, enabling positron emission tomography (PET) imaging, which reveals efficient tumor accumulation and rapid renal clearance of WGA-PEG CPNs upon intravenous injection. Utilizing the radio-sensitizing function of tungsten with strong X-ray absorption, such W-GA-PEG CPNs were able to greatly enhance the efficacy of cancer radiotherapy in inhibiting the tumor growth. With fast clearance and little long-term body retention, those W-GA-PEG CPNs exhibited no appreciable in vivo toxicity. This study presents a type of CPNs with excellent imaging and therapeutic abilities as well as rapid renal clearance behavior, promising for further clinic translation.