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

Abstract

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 177Lu (177Lu-SPN-GIP) for combined radio- and photothermal therapy of pancreatic tumor. 177Lu-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), 177Lu-SPN-GIP exhibited enhanced therapeutic capability to kill cancer cells and xenograft tumor in living mice compared with RT or PTT alone. More importantly, 177Lu-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. Graphical abstract

Recent Advances in Well-Designed Therapeutic Nanosystems for the Pancreatic Ductal Adenocarcinoma Treatment Dilemma

“…In vitro and in vivo experiments showed that the combined treatment could effectively combat PDAC and improve the therapeutic effect. Semiconductor polymer NPs (SPN) composed of completely organic compounds have become photothermal agents for cancer treatment [ 119 , 120 ]. Compared with other inorganic nanomaterials, SPNs have unique characteristics such as better biocompatibility, and higher photothermal conversion efficiency and controllability.…”

“…The utilization of SPNs for PTT has been well explored, but there are few reports on combination therapy. In their study, Shi et al reported a 177 Lu-labeled glucose-dependent insulinotropic polypeptide-targeting SPN for combined radiotherapy and PTT of PDAC [ 120 ]. As a result, these combined treatment techniques complemented each other and provided superior results to PTT or radiotherapy alone.…”

Development of nanotechnology-mediated precision radiotherapy for anti-metastasis and radioprotection

“…, 131 I, 99m Tc, and 177 Lu) to observe pharmacokinetics and biodistribution of radioactive drugs. 361–363 For instance, Cheng et al designed radioisotope 131 I-labeled Au nanoframeworks ( 131 I-AuNFs) for synergistic RIT/PTT of breast cancer. 364 Specifically, the AuNFs were coated with polydopamine (PDA) and further chelated with 131 I to construct 131 I-AuNFs (Fig.…”

Ionizing Radiation-Induced Ferroptosis Based on Nanomaterials

“… 54 Shi et al designed a nano-radiopharmaceutical ( 177 Lu-SPN-GIP) that displayed greater tumor-killing impact than conventional RT and considerably improved therapeutic outcomes. 55 Consequently, combining nanomaterials-induced ferroptosis and ionizing radiation will be a viable approach. Because it can improve stability, cell uptake rate and tumor site retention time.…”