Semiconducting polymer nano-radiopharmaceutical for combined radio-photothermal therapy of pancreatic tumor

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.

Automated summary

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.