Surface Nanotube Engineering of Iodine‐125 Seed for Combination of Chemotherapy and Brachytherapy

Abstract Iodine‐125 ( 125 I) brachytherapy, in combination with chemotherapy, is extensively utilized for tumor treatment. However, the primary challenge in concurrently implementing brachy‐chemotherapy involves integrating the in situ implantation of 125 I seeds with the systematic administration of chemotherapeutic agents. Therefore, a novel 125 I seed modified with titanium dioxide nanotubes ( 125 I@TNT) is proposed to establish a localized drug release system. The titanium dioxide nanotubes are fabricated through anodic oxidation, exhibiting a uniform diameter of ≈100 nm and a thickness of 1 µm. These nanotubes effectively loaded doxorubicin (29.16 µg DOX/seed) while meeting the quality standards for subsequent applications, such as outer diameter and leak‐proofness properties ( 125 I@TNT loaded with DOX is named 125 I@TNT‐DOX). In vivo distribution studies revealed that 125 I@TNT‐DOX delivered significantly more DOX concentrations to tumors compared to free DOX administered intravenously (5 mg kg −1 ) while delivering less DOX in the heart. Both in vitro and in vivo studies confirmed that apoptosis is the primary mechanism of cell death induced by 125 I@TNT‐DOX. Additionally, 125 I@TNT‐DOX effectively suppressed the growth of subcutaneous tumors in 4T1 and Hepa1‐6 tumor‐bearing mouse, surpassing other treatments, particularly the combination of 125 I seeds and intravenously administered DOX (5 mg kg −1 ). This system offers a promising strategy for enhancing concurrent brachy‐chemotherapy.