Jie Lyu,Long Qiu,Fuyuan Tan,Yuying Yu,Xisheng Fan,Tianzhen Ye,Shuran Lei,Jiali Liao,Yuanyou Yang,Ning Liu,Feize Li
Despite the advances in the use of nanodrug delivery systems (NDDS) in anticancer investigations, their clinical practice has long been limited by the undesirable uptake of nanocarriers via the mononuclear phagocyte system (MPS). Leveraging the unique in vivo behaviors of NDDS to treat tumors located in MPS-associated organs offers a promising alternative to circumvent this limitation, yet rational designs to improve the accumulation of nanocarriers in target tissues are strongly desirable. Here, we propose a simple and efficient strategy to regulate the retention of radiolabeled NDDS in MPS-associated organs through surface modification, enhancing its potential of targeted radionuclide therapy (TRT) for metastatic lung cancer. 1,2-dioleoyl-sn-glycero-3-phosphate (DOPA) was employed to modify the surface properties of 224 Ra radiolabeled nanohydroxyapatite ( 224 Ra-nHAP), with an attempt to achieve targeted delivery and localization of the radionuclide cytotoxin. The prepared 224 Ra-nHAP@DOPA has been well characterized, exhibiting good micromorphology, optimal radiochemical stability, enhanced cytotoxicity, and high lung retention. As a result, fractioned administration of 224 Ra labeled nHAP@DOPA (18.50 kBq × 3) could markedly suppress metastatic lung tumor growth (82.92 % inhibition of nodules), prolonging the survival in murine metastatic cancer models. These findings highlight the potential of NDDS in treating tumors in MPS-associated organs via tailored surface modification of the nanosized carrier, providing valuable insights for the development of nanomedicine and TRT.
212 Pb serves as one of the most important nuclides for targeted alpha therapy (TAT), with good potential in the treatment of malignant tumors. However, medical and clinical applications are seriously limited by its extremely short supply, which strongly depends on the acquisition of its parent nuclides such as 228 Ra or 224 Ra. To address this issue, we conducted a systematic investigation on the separation of trace radium from natural thorium using the ion exchange chromatography method, and a novel porous silica-based composite resin functionalized with sulfonic acid groups was prepared, characterized, and employed. Experimental results showed that the silica-supported resin was successfully prepared with the sulfonic acid groups, and possessed small particle size, mesoporous pore structure and large specific surface area. The resin exhibited high selectivity toward thorium compared with barium, and the separation factor reached 123 at low acidity and at low temperature. The resin demonstrated a fast adsorption speed and an excellent separation performance, and the adsorption mechanism was confirmed based on the ion exchange between the sodium carried and the target cations. On the basis, column experiments were further conducted and finally the separation of trace radium from thorium was realized using a small column filled with about 1.0 g resin. The chemical recovery of radium reached 97 %, and the decontamination factor for thorium exceeded 40,000. This work verifies the feasibility of directly extracting 228 Ra and 224 Ra from natural thorium using the sulfonic acid group functionalized materials in the dilute nitric acid solution, and presents an excellent material and systematic experimental data on the separation activities, rendering this study particularly significant.
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