Nanoagents Based on Poly(ethylene glycol)-b-Poly(L-thyroxine) Block Copolypeptide for Enhanced Dual-Modality Imaging and Targeted Tumor Radiotherapy
Xiaolei Gu1, Zhehong Zhu1, Qianyi Fan1, Yaohua Wei1, Guanglin Wang2, Fenghua Meng1, Zhiyuan Zhong1,*（钟志远）, and Chao Deng1,*（邓超）
1Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application College of Chemistry, Chemical Engineering and Materials Science and State Key Laboratory of Radiation Medicine and Protection Soochow University
Suzhou 215123, China
2School of Radiation Medicine and Protection and School for Radiological and Interdisciplinary Sciences Medical College of Soochow University Suzhou 215123, China
Small 2019, 1902577
Future healthcare requires development of novel theranostic agents that are capable of not only enhancing diagnosis and monitoring therapeutic responses but also augmenting therapeutic outcomes. Here, a versatile and stable nanoagent is reported based on poly(ethylene glycol)-b-poly(Lthyroxine) (PEG-PThy) block copolypeptide for enhanced single photon emission computed tomography/computed tomography (SPECT/CT) dual-modality imaging and targeted tumor radiotherapy in vivo. PEG-PThy acquired by polymerization of L-thyroxine-N-carboxyanhydride (Thy-NCA) displays a controlled Mn, high iodine content of _49.2 wt%, and can spontaneously form 65 nm-sized nanoparticles (PThyN). In contrast to clinically used contrast agents like iohexol and iodixanol, PThyN reveals iso-osmolality, low viscosity, and long circulation time. While PThyN exhibits comparable in vitro CT attenuation efficacy to iohexol, it greatly enhances in vivo CT imaging
of vascular systems and soft tissues. PThyN allows for surface decoration
with the cRGD peptide achieving enhanced CT imaging of subcutaneous B16F10 melanoma and orthotopic A549 lung tumor. Taking advantages of a facile iodine exchange reaction, 125I-labeled PThyN enables SPECT/CT imaging of tumors and monitoring of PThyN biodistribution in vivo. Besides, 131I-labeled and cRGD-functionalized PThyN displays remarkable growth inhibition of the B16F10 tumor in mice (tumor inhibition rate > 89%). These poly(L-thyroxine) nanoparticles provide a unique and versatile theranostic platform for varying diseases.
链接：https://doi.org/10.1002/smll.201902577