An Jie, Chu Kaile, Li Xirong, Ma Huizhu, Zhou Qin, Niu Chenliang, Gao Jie, Lv Junping, Cao Jianbo, Zhang XinYu, Zhou Haitao, Wang Hongliang, Li Min, Wu Zhifang, Li Sijin
Department of Nuclear Medicine, The First Hospital of Shanxi Medical University, Shanxi Medical University, Taiyuan, 030001, Shanxi, People's Republic of China.
Shanxi Key Laboratory of Molecular Imaging, Shanxi Medical University, Taiyuan, 030001, Shanxi, People's Republic of China.
J Nanobiotechnology. 2025 Jul 24;23(1):539. doi: 10.1186/s12951-025-03611-8.
Radionuclide therapy and chemotherapy are effective for pancreatic cancer, yet their efficacy is often limited by tumor hypoxia. In this study, manganese porphyrin (MnTTP) and tirapazamine (TPZ) were encapsulated in polylactic-co-glycolic acid (PLGA) spheres, which were subsequently coated with polydopamine to label the radionuclide I, forming a theranostic nanoplatform. The nanoplatform demonstrated excellent biocompatibility, stable labeling efficiency, and dual-modal MRI/SPECT imaging capabilities. The nanoplatform generated reactive oxygen species (ROS) under ultrasound(US) activation, in combination with the β-rays emitted by I, synergistically eradicate tumor cells and exacerbate hypoxia in the tumor microenvironment. Furthermore, TPZ was activated to produce toxic free radicals under hypoxic conditions, enabling a synergistic therapeutic approach that combined radionuclide therapy and sonodynamic therapy. This approach effectively inhibited tumor stem cell formation and enhanced anti-tumor efficacy. Additionally, the nanoplatform's metabolism in vivo and the therapeutic effect were monitored in real-time under MRI/SPECT dual-modality imaging. This therapeutic strategy offers a promising solution for overcoming tumor hypoxia and achieving efficient combination therapy for tumors.
放射性核素疗法和化学疗法对胰腺癌有效，但其疗效常常受到肿瘤缺氧的限制。在本研究中，锰卟啉（MnTTP）和替拉扎明（TPZ）被包裹于聚乳酸-羟基乙酸共聚物（PLGA）微球中，随后用聚多巴胺进行包被以标记放射性核素碘，从而形成一种诊疗纳米平台。该纳米平台表现出优异的生物相容性、稳定的标记效率以及双模态磁共振成像/单光子发射计算机断层扫描成像能力。该纳米平台在超声（US）激活下产生活性氧（ROS），并与碘发射的β射线相结合，协同根除肿瘤细胞并加剧肿瘤微环境中的缺氧状况。此外，TPZ在缺氧条件下被激活以产生有毒自由基，从而实现一种将放射性核素疗法与声动力疗法相结合的协同治疗方法。这种方法有效抑制肿瘤干细胞形成并增强抗肿瘤疗效。此外，在磁共振成像/单光子发射计算机断层扫描双模态成像下实时监测该纳米平台在体内的代谢情况及治疗效果。这种治疗策略为克服肿瘤缺氧及实现肿瘤的高效联合治疗提供了一种有前景的解决方案。
