机构：[1]State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, China.[2]School of Physical Science and Technology, ShanghaiTech University, Shanghai 201210, China.[3]Fujian Science & Technology Innovation Laboratory for Optoelectronic Information of China, Fuzhou, Fujian 350108, China.[4]Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian 362000, China.[5]Key Laboratory of Radiation Physics and Technology of the Ministry of Education, Institute of Nuclear Science and Technology, Sichuan University, Chengdu, Sichuan 610064, China.
Cancer remains a global health challenge, with current postoperative adjuvant therapies for advanced solid tumors being limited by therapeutic resistance, off-target effects, and insufficient treatment monitoring. Here, we report a rational design of a novel tumor-targeted 177Lu-labeled lanthanide nanoradiopharmaceutical called 177Lu-LnNRP@HER2 (namely, NaGdF4:Yb@NaErF4:Tm@NaYF4:Yb/177Lu@NaYF4@DSPE-PEG-HER2). This nanoradiopharmaceutical is engineered to enable precision postoperative β-radiotherapy in combination with real-time radiation-free prognosis monitoring. The unique multilayer structure of 177Lu-LnNRP@HER2 simultaneously facilitates tumor-selective β-particle irradiation through stably labeled 177Lu for eliminating residual tumor cells and provides strong upconversion/near-infrared-II (UC/NIR-II) fluorescent signals for intraoperative tumor margin delineation and postoperative monitoring. In an orthotopic gastric tumor model, 177Lu-LnNRP@HER2 demonstrates significant postoperative therapeutic efficacy and real-time prognosis monitoring capability, achieving an 84% suppression of recurrence, an 88.6% reduction in metastasis, and a 2.6-fold increase in median survival. Multimodal analyses, including high-resolution cell imaging, flow cytometry, and transcriptomics, reveal that the excellent antitumor activity of 177Lu-LnNRP@HER2 is mainly attributed to the DNA damage and reactive oxygen species elevation arising from the proximity-targeted β-particle irradiation of tumor cell nuclei and mitochondria. These findings address a key gap in the field by synchronizing targeted radionuclide therapy with integrated real-time monitoring, thus promising a new paradigm for precision oncology.
基金：
This work is supported by the Major Research plan of the
National Natural Science Foundation of China (Grant No.
92361202), National Natural Science Foundation of China
(No. 12204481), Fund of Fujian Science & Technology
Innovation Laboratory for Optoelectronic Information
(2020ZZ114), Natural Science Foundation of Fujian Province
(Nos. 2022J05102 and 2024J09062), National Key Research
and Development Program of China (2022YFB3503700 and
2023YFF0713605), and Self-deployment Project Research
Program of Haixi Institutes, Chinese Academy of Sciences
(CXZX-2022-GS01).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2025]版：
大类|1 区化学
小类|1 区化学：综合
最新[2025]版：
大类|1 区化学
小类|1 区化学：综合
第一作者：
第一作者机构：[1]State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, China.[2]School of Physical Science and Technology, ShanghaiTech University, Shanghai 201210, China.
通讯作者：
通讯机构：[1]State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, China.[2]School of Physical Science and Technology, ShanghaiTech University, Shanghai 201210, China.[3]Fujian Science & Technology Innovation Laboratory for Optoelectronic Information of China, Fuzhou, Fujian 350108, China.
推荐引用方式(GB/T 7714)：
Zheng Jingwen,Chen Hao,Zhang Hongyun,et al.Constructing 177Lu-Labeled Lanthanide Nano-Radiopharmaceuticals for Efficient Postoperative Tumor Radionuclide Therapy and Prognosis Monitoring[J].Journal Of The American Chemical Society.2025,147(45):41913-41923.doi:10.1021/jacs.5c14832.
APA：
Zheng Jingwen,Chen Hao,Zhang Hongyun,Wu Zhifen,Ye Lixiang...&Hong Maochun.(2025).Constructing 177Lu-Labeled Lanthanide Nano-Radiopharmaceuticals for Efficient Postoperative Tumor Radionuclide Therapy and Prognosis Monitoring.Journal Of The American Chemical Society,147,(45)
MLA：
Zheng Jingwen,et al."Constructing 177Lu-Labeled Lanthanide Nano-Radiopharmaceuticals for Efficient Postoperative Tumor Radionuclide Therapy and Prognosis Monitoring".Journal Of The American Chemical Society 147..45(2025):41913-41923
化学