211At-Labeled Polymer Nanoparticles for
Targeted Radionuclide Therapy of Glucose-Dependent Insulinotropic
Polypeptide Receptor (GIPR)-Overexpressed Cancer
posted on 2021-07-14, 22:13authored byXiumin Shi, Qing Li, Lulu Zhang, Masayuki Hanyu, Lin Xie, Kuan Hu, Kotaro Nagatsu, Chuan Zhang, Zhengcan Wu, Feng Wang, Ming-Rong Zhang, Kai Yang, Ran Zhu
Targeted
radionuclide therapy (TRT) provides new and safe opportunities
for cancer treatment and management with high precision and efficiency.
Here we have designed a novel semiconducting polymer nanoparticle
(SPN)-based radiopharmaceutical (211At-MeATE-SPN-GIP) for
TRT against glucose-dependent insulinotropic polypeptide receptor
(GIPR)-positive cancers to further explore the applications of nanoengineered
TRT. 211At-MeATE-SPN-GIP was engineered via nanoprecipitation,
followed by its functionalization with a glucose-dependent insulinotropic
polypeptide (GIP) to target GIPR and deliver 211At for
α therapy. The therapeutic effect and biological safety of 211At-MeATE-SPN-GIP were investigated using GIPR-overexpressing
human pancreatic cancer CFPAC-1 cells and CFPAC-1-bearing mice. In
this work, 211At-MeATE-SPN-GIP was produced with a radiochemical
yield of 43% and radiochemical purity of 98%, which exhibited a specifically
high uptake in CFPAC-1 cells, inducing cell cycle arrest at the G2/M
phase and extensive DNA damage. In the CFPAC-1-bearing tumor model, 211At-MeATE-SPN-GIP exhibited high therapeutic efficiency,
with no obvious side effects. The GIPR-specific binding of 211At-MeATE-SPN-GIP combined with effective inhibition of tumor growth
and fewer side effects compared to control suggests that 211At-MeATE-SPN-GIP TRT holds great potential as a novel nanoengineered
TRT strategy for patients with GIPR-positive cancer.