224Ra labeled nanohydroxyapatite for targeted alpha therapy of metastatic lung cancer

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.