纳米抗体由于其出色的体内特性而成为有前途的载体。靶向编程性细胞死亡配体1（PD-L1）的放射性药物治疗是一种有效的治疗策略。我们的研究旨在探索131I标记的PD-L1纳米抗体（Nb109）在非小细胞肺癌（NSCLC）体外和体内的治疗效果。通过氯胺T法合成了131I-Nb109。我们实施了稳定性分析、SDS-PAGE和脂水分配系数测试来评估其质量。应用细胞摄取试验和SPECT / CT扫描来评估其靶向NSCLC（H460和A549）的能力。进行了CCK8试验和体内疗效试验来评估其在H460肿瘤中的治疗作用。通过Western印迹和ATP试剂盒调查了在孵育有131I-Nb109的H460细胞中的损伤相关分子模式（DAMPs）释放。131I-Nb109具有高的标记率（69.51-98.06％），放射化学纯度（99.17％±0.76％）和稳定性，是亲水性的。细胞摄取实验表明，H460细胞（PD-L1阳性）相对于A549细胞（PD-L1阴性）具有更高的131I-Nb109摄取率。SPECT / CT成像显示在48小时内131I-Nb109在H460肿瘤中的积累。131I-Nb109抑制了H460肿瘤的生长，与对照组相比没有毒副作用。它还诱导H460细胞释放DAMPs（三磷酸腺苷，高迁移率族蛋白1和热休克蛋白70）。131I-Nb109具有高的稳定性，出色的针对和治疗PD-L1阳性肿瘤的能力，可以提高肿瘤的免疫原性。我们研究的结果有望激发更多新型放射性药物治疗NSCLC的发展。© 2023作者（们），在Springer-Verlag GmbH Germany的独家许可下，Springer Nature的一部分。

Nanobodies have become promising carriers due to excellent in vivo properties. Radiopharmaceutical therapy targeting programmed cell death ligand 1 (PD-L1) is an effective therapeutic strategy. Our study aimed to explore therapeutic efficacy of 131I labeled PD-L1 nanobody (Nb109) in non-small cell lung cancers (NSCLCs) in vitro and in vivo.131I-Nb109 was synthesized by chloramine-T method. We implemented stability analysis, SDS-PAGE and lipid-water partition coefficient test to assess its quality. Cell uptake assay and SPECT/CT scan were applied to evaluate its ability to target NSCLCs (H460 and A549). CCK8 assay and in vivo efficacy assay were conducted to estimate its therapeutic effect in H460 tumors. Damage-associated molecular patterns (DAMPs) release in H460 cells incubated with 131I-Nb109 was investigated by western blot and ATP test kit.131I-Nb109 was hydrophilic with high labeling rate (69.51-98.06%), radiochemical purity (99.17% ± 0.76%) and stability. Cell uptake experiments showed that H460 cells (PD-L1 positive) compared with A549 cells (PD-L1 negative) had higher 131I-Nb109 uptake. SPECT/CT imaging revealed the accumulation of 131I-Nb109 in H460 tumor within 48 h. 131I-Nb109 inhibited H460 tumor growth without toxic side effects in contrast with control group. It also induced H460 cells to release DAMPs (adenosine triphosphate, high mobility group box 1, and heat shock protein 70).131I-Nb109 had high stability, excellent ability to target and treatment PD-L1 positive tumors, and can improve tumor immunogenicity. The results of our study were expected to inspire the development of more novel radiopharmaceuticals to treat NSCLCs.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.