Radionuclide therapy is an important form of tumor internal radiation therapy (IRT), but its curative effect is restricted by the low radiation intensity and poor targeting ability of nuclides, which hampers efficient killing of DNA. Moreover, the limited penetration depth and nonuniform dose distribution of rays result in “blind” regions with residual living cancer cells, which increases the risk of tumor metastasis. Herein, we developed a new strategy to tactfully incorporate IRT with immunotherapy to achieve highly efficient synergistic therapy. Specifically, gold nanoparticles (AuNPs) co-modified with radioactive iodine-131 and the twin arginine translocation (TAT) peptide (¹³¹I-AuNPs-TAT) were constructed, in which TAT-guided nuclei targeting provided highly concentrated β-rays to the most radiosensitive DNA. Meanwhile, β⁻ electrons dashed on AuNPs with a sudden drop in speed can transform into low-dosage X-ray bremsstrahlung radiation. X-rays have a longer penetration depth than β-rays and are able to induce a strong immune response, thus eliminating the area that is blind to short-range β-rays resulting from the limited dose distribution. This method, named “internal radio-immunity therapy (IRIT)”, is a unique approach that combines IRT with immunotherapy to not only enhance radiotherapeutic efficacy but also broaden the clinical applications of ¹³¹I, thereby demonstrating great potential for scientific research and clinical applications.

中文翻译：

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放射性核素标记的金纳米颗粒，用于靶向核的内部放射免疫治疗

放射性核素疗法是肿瘤内部放射疗法（IRT）的一种重要形式，但其治疗效果受到核素低放射强度和较弱的靶向能力的限制，这阻碍了DNA的有效杀伤。此外，有限的射线穿透深度和不均匀的射线分布会导致“盲”区带有残留的活癌细胞，从而增加了肿瘤转移的风险。本文中，我们开发了一种新策略，将IRT与免疫疗法巧妙地结合在一起，以实现高效的协同治疗。具体而言，金纳米颗粒（AuNPs）与放射性碘131和双精氨酸易位（TAT）肽共修饰（¹³¹构建了I-AuNPs-TAT），其中TAT引导的核靶向为最放射敏感性的DNA提供了高度浓缩的β射线。另一方面，β ^-虚线上的AuNP与速度的突然下降的电子可以转变成低剂量X射线轫致辐射的辐射。X射线具有比β射线更长的穿透深度，并且能够诱导强烈的免疫反应，因此消除了由于有限的剂量分布而对短距离β射线不可见的区域。该方法被称为“内部放射免疫疗法（IRIT）”，是一种将IRT与免疫疗法相结合的独特方法，不仅可以增强放射治疗的功效，而且可以拓宽¹³¹ I的临床应用范围，从而证明了在科学研究和临床应用中的巨大潜力。