三阴性乳腺癌（TNBC）是预后最差的乳腺癌亚型。放射治疗（RT）是该疾病的核心治疗方法之一；然而，RT的电离辐射具有严重的副作用。以更低的放射剂量达到更好的治疗效果是放疗的一贯发展方向。研究表明，放疗与光疗、磁疗等非电离放射治疗相结合，可以产生协同效应，从而达到减少剂量、增强疗效的目的。在本研究中，我们应用具有磁热功能和光疗功能的FeCo纳米粒子剂 IR-780 构建电离和非电离辐射协同纳米颗粒（INS NP）。 INS NP 首先进行形貌、尺寸、胶体稳定性、负载能力和光热转换测试。随后，使用体外细胞系评估细胞抑制和细胞内化。在全面评估纳米粒子的体内生物相容性后，建立荷瘤小鼠模型，以评估其体内分布、靶向递送和抗肿瘤效果。INS 纳米粒子的饱和磁化强度超过 72 emu/g，即流体动力学粒径约 40 nm，带负电的表面，以及良好的胶体稳定性和封装性能。 INS NP 保持了 IR-780 在 808 nm 处的光谱特性。在激光照射下，最高温度为92°C，INS NPs也达到了体内有效热温度。体内和体外试验均证明INS NPs具有良好的生物相容性。 INS NPs在体内注射一次后保持有效一周以上，并且还可以通过永磁体在肿瘤中引导和积累。随后的结果显示，在低剂量放疗和激光照射下，联合干预组表现出显着的协同效应，ROS产生率远高于放疗和光疗治疗组。在小鼠模型中，60%的肿瘤被完全根除。INS NPs有效克服了TNBC放疗的诸多缺点，为开发TNBC新型临床治疗方法提供了实验基础。© 2024。作者。

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with the worst prognosis. Radiotherapy (RT) is one of the core modalities for the disease; however, the ionizing radiation of RT has severe side effects. The consistent development direction of RT is to achieve better therapeutic effect with lower radiation dose. Studies have demonstrated that synergistic effects can be achieved by combining RT with non-ionizing radiation therapies such as light and magnetic therapy, thereby achieving the goal of dose reduction and efficacy enhancement.In this study, we applied FeCo NPs with magneto thermal function and phototherapeutic agent IR-780 to construct an ionizing and non-ionizing radiation synergistic nanoparticle (INS NPs). INS NPs are first subjected to morphology, size, colloidal stability, loading capacity, and photothermal conversion tests. Subsequently, the cell inhibitory and cellular internalization were evaluated using cell lines in vitro. Following comprehensive assessment of the NPs' in vivo biocompatibility, tumor-bearing mouse model was established to evaluate their distribution, targeted delivery, and anti-tumor effects in vivo.INS NPs have a saturation magnetization exceeding 72 emu/g, a hydrodynamic particle size of approximately 40 nm, a negatively charged surface, and good colloidal stability and encapsulation properties. INS NPs maintain the spectral characteristics of IR-780 at 808 nm. Under laser irradiation, the maximum temperature was 92 °C, INS NPs also achieved the effective heat temperature in vivo. Both in vivo and in vitro tests have proven that INS NPs have good biocompatibility. INS NPs remained effective for more than a week after one injection in vivo, and can also be guided and accumulated in tumors through permanent magnets. Later, the results exhibited that under low-dose RT and laser irradiation, the combined intervention group showed significant synergetic effects, and the ROS production rate was much higher than that of the RT and phototherapy-treated groups. In the mice model, 60% of the tumors were completely eradicated.INS NPs effectively overcome many shortcomings of RT for TNBC and provide experimental basis for the development of novel clinical treatment methods for TNBC.© 2024. The Author(s).