期刊
JOURNAL OF NANOBIOTECHNOLOGY
卷 19, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s12951-021-01083-0
关键词
Semiconducting polymer nanoparticles (SPNs); Radiopharmaceuticals; Pancreatic cancer; Combined therapy; Radiotherapy; Photothermal therapy
资金
- National Key Research Program of China [2018YFA0208800]
- National Natural Science Foundation of China [22076132, 21976128]
- Natural Science Foundation of Jiangsu Province [BK20200100, BK20190830]
- Suzhou Administration of Science Technology [SYS2020082]
- Project of State Key Laboratory of Radiation Medicine and Protection, Soochow University [GZK1201806]
A semiconducting polymer nano-radiopharmaceutical labeled with therapeutic radioisotope Lu-177 (Lu-177-SPN-GIP) was developed for combined radio- and photothermal therapy of pancreatic tumor, showing enhanced therapeutic capability compared to individual treatments. Lu-177-SPN-GIP demonstrated strong cell uptake, long retention in tumor site, and the ability to suppress tumor stem cell growth and reverse EMT, potentially reducing metastasis.
Background: Pancreatic ductal adenocarcinoma (PDAC) is a devastatingly malignant tumor with a high mortality. However, current strategies to treat PDAC generally have low efficacy and high side-effects, therefore, effective treatment against PDAC remains an urgent need. Results: We report a semiconducting polymer nano-radiopharmaceutical with intrinsic photothermal capability and labeling with therapeutic radioisotope Lu-177 (Lu-177-SPN-GIP) for combined radio- and photothermal therapy of pancreatic tumor. Lu-177-SPN-GIP endowed good stability at physiological conditions, high cell uptake, and long retention time in tumor site. By virtue of combined radiotherapy (RT) and photothermal therapy (PTT), Lu-177-SPN-GIP exhibited enhanced therapeutic capability to kill cancer cells and xenograft tumor in living mice compared with RT or PTT alone. More importantly, Lu-177-SPN-GIP could suppress the growth of the tumor stem cells and reverse epithelial mesenchymal transition (EMT), which may greatly reduce the occurrence of metastasis. Conclusion: Such strategy we developed could improve therapeutic outcomes over traditional RT as it is able to ablate tumor with relatively lower doses of radiopharmaceuticals to reduce its side effects.
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