Strong Affinity between Astatine and Silver: An Available Approach to Anchoring 211At in Nanocarrier for Locoregional Oncotherapy.

Recently, ²¹¹At-related endoradiotherapy has emerged as an important oncotherapy strategy. Conjugating ²¹¹At with a nanocarrier provides a vital candidate for radionuclide therapy of various malignant tumors. In this study, we proposed utilizing the intrinsically high affinity of heavy halogens and sulfhydryl compounds for metallic silver to achieve highly efficient conjugation between ²¹¹At and Ag-based nanoparticles in a simple way. ²¹¹At@Ag-PEG-FA was obtained via a one-pot assembly of ²¹¹At, Ag, and SH-PEG-FA in extremely high radiolabeling yield (>95%) within 15 min and maintained excellent stability in simulated physiochemical media. Additionally, the prepared ²¹¹At@Ag-PEG-FA demonstrated specific binding to the breast cancer cell line (4T1), with a high endocytosis rate and low reflux, leading to significant cell growth inhibition. ²¹¹At@Ag-PEG-FA exhibits an excellent antitumor effect that completely suppressed tumor growth during the first week, effectively prolonging the median survival of mice to 44 days, relative to 18 days in the control group. All of the mice exhibited minimal side effects from ²¹¹At@Ag-PEG-FA in the experiment, indicating its acceptable biosafety. Our work shows that the strong affinity of Ag can be utilized to produce radioactivated nanomedicines with excellent stability and high efficiency, which also provides some valuable insights for the ²¹¹At radiolabeling of general compounds.