Tumor microenvironment-responsive precise delivery nanocarrier potentiating synchronous radionuclide therapy and chemotherapy against cancer.

To achieve better therapeutic outcomes in cancer treatment, the combination of radionuclide and chemotherapy is commonly employed in clinical practice. However, the primary challenge lies in achieving precise drug delivery to tumor tissues, often leading to suboptimal therapeutic efficacy. This study presents a novel, tumor microenvironment-responsive drug delivery carrier that integrates real-time MRI/SPECT dual-modal imaging for precise diagnosis and treatment monitoring. The carrier comprised is based on a hybrid structure composed of hyaluronic acid (HA) and human serum albumin (HSA), encapsulating the metal-organic framework MIL-100(Fe). It was loaded with the chemotherapeutic drug doxorubicin (DOX) and modified with the radionuclide I, designed to precise diagnosis and treatment of tumors. HA binds specifically to the overexpressed CD44 receptor on the tumor surface, ensuring that the carrier targets tumors selectively. The incorporated I emits β rays, which deliver ionizing radiation to eradicate tumor cells. Concurrently, the carrier could release DOX in response to the tumor microenvironment, inhibiting DNA synthesis and sensitizing the tumor cells to radiation. This combined approach results in synchronous radionuclide therapy (RNT) and chemotherapy, maximizing therapeutic impact. In vitro and in vivo experiments demonstrated that the carrier exhibited favorable biocompatibility, stable radionuclide labeling, tumor-specific accumulation, and controlled release of DOX within the tumor microenvironment. Furthermore, MRI/SPECT dual-modal imaging enabled real-time tumor localization and monitoring of the carrier in vivo biodistribution. Experimental outcomes confirmed that this innovative carrier, combining RNT and chemotherapy, significantly inhibited tumor growth. This strategy offers a promising approach for precision radio-chemotherapy guided by dual-modal imaging, providing valuable insights for integrated targeted diagnosis and treatment of tumors.