Renal-Clearable Ultrasmall Coordination Polymer Nanodots for Chelator-Free 64Cu-Labeling and Imaging-Guided Enhanced Radiotherapy of Cancer.

Abstract

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 imaging-guided 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 W-GA-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.

• Authors: Sida Shen, Dawei Jiang, Liang Cheng, Yu Chao, Kaiqi Nie, Ziliang Dong, Christopher J Kutyreff, Jonathan W Engle, Peng Huang, Weibo Cai, Zhuang Liu
• Journal: ACS nano (ACS Nano) Vol. 11 Issue 9 Pg. 9103-9111 (09 26 2017) ISSN: 1936-086X [Electronic] United States
• PMID: 28853861 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Coordination Complexes
• Copper Radioisotopes
• Copper-64
• Polyethylene Glycols
• Gallic Acid
• Tungsten

Topics

• Animals
• Breast Neoplasms (diagnostic imaging, metabolism, radiotherapy)
• Cell Line, Tumor
• Coordination Complexes (chemistry, pharmacokinetics, therapeutic use)
• Copper Radioisotopes (chemistry, pharmacokinetics, therapeutic use)
• Female
• Gallic Acid (analogs & derivatives, pharmacokinetics, therapeutic use)
• Kidney (metabolism)
• Mice
• Nanoparticles (chemistry, therapeutic use)
• Polyethylene Glycols (chemistry, pharmacokinetics, therapeutic use)
• Positron-Emission Tomography (methods)
• Tissue Distribution
• Tungsten (chemistry, pharmacokinetics, therapeutic use)