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

作者：Jie An, Qin Zhou, Kaile Chu, Siyuan Chen, Chenliang Niu, Weimin Zhang, Jie Gao, Man Li, Jianbo Cao, Junping Lv, Di Zhang, Zhifang Wu, Sijin Li, Hua Wei · 发表于：Journal of Nanobiotechnology · 年份：2025 · DOI：10.1186/s12951-025-03364-4 · 被引用次数：16 · 研究领域：Nanoplatforms for cancer theranostics、Radiopharmaceutical Chemistry and Applications、Boron Compounds in Chemistry

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 131 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 131 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 relea...