Strong Affinity\nbetween Astatine and Silver: An Available\nApproach to Anchoring <sup>211</sup>At in Nanocarrier for Locoregional\nOncotherapy

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