Deng Caiting, Zhang Jingjing, Yang Yuchen, Ding Yuhan, An Feifei, Wang Fu
Institute of Medical Engineering, School of Basic Medical Science, Health Science Center, Xi'an Jiaotong University, No. 76 Yanta West Road, Xi'an, Shaanxi, 710061, China.
School of Public Health, Health Science Center, Xi'an Jiaotong University, No.76 Yanta West Road, Xi'an, Shaanxi, 710061, China.
Small. 2025 Jul;21(27):e2503117. doi: 10.1002/smll.202503117. Epub 2025 May 16.
Iodine-131 (I), a cornerstone of thyroid cancer therapy, suffers from limited efficacy in other cancers due to poor tumor accumulation and hypoxia-driven radiotherapy resistance. To overcome these challenges, I-M@HI, a theranostic nanoparticle was engineered that synergizes radiotherapy with chemodynamic therapy (CDT). This platform integrated Mn(III) porphyrin and indocyanine green self-assembled on albumin, enabling dual-mode fluorescence/MRI-guided imaging, tumor/sentinel lymph node-targeted accumulation, and hypoxia modulation. The Mn(III) porphyrin catalyzes intratumoral hydrogen peroxide into cytotoxic hydroxyl radicals for CDT while alleviating hypoxia to amplify I radiotherapy. In subcutaneous tumors, I-M@HI achieved >85% tumor inhibition by inducing immunogenic cell death, marked by calreticulin exposure and high mobility group box 1 release, and triggered systemic anti-tumor immunity. Strikingly, in a breast cancer metastasis model, I-M@HI selectively eradicated sentinel lymph node metastases, reducing lung metastatic nodules by >90%, representing a critical advancement for preventing metastatic spread. This work pioneers a multifunctional nanoplatform that not only enhances radiotherapy but also redefines precision metastasis inhibition, offering a transformative strategy for advanced cancer therapy.
碘 - 131（I）是甲状腺癌治疗的基石，但由于肿瘤摄取不佳和缺氧驱动的放疗抗性，在其他癌症中的疗效有限。为了克服这些挑战，设计了一种治疗诊断纳米颗粒I - M@HI，它将放射治疗与化学动力疗法（CDT）协同作用。该平台将锰（III）卟啉和吲哚菁绿整合在白蛋白上自组装，实现双模式荧光/MRI引导成像、肿瘤/前哨淋巴结靶向积累和缺氧调节。锰（III）卟啉将肿瘤内的过氧化氢催化成具有细胞毒性的羟基自由基用于CDT，同时缓解缺氧以增强I放射治疗。在皮下肿瘤中，I - M@HI通过诱导免疫原性细胞死亡实现了>85%的肿瘤抑制，其特征为钙网蛋白暴露和高迁移率族蛋白B1释放，并触发了全身抗肿瘤免疫。引人注目的是，在乳腺癌转移模型中，I - M@HI选择性地根除了前哨淋巴结转移，使肺转移结节减少>90%，这代表了预防转移扩散的一项关键进展。这项工作开创了一种多功能纳米平台，不仅增强了放射治疗，还重新定义了精确转移抑制，为晚期癌症治疗提供了一种变革性策略。
