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Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: INS NPs effectively overcome many shortcomings of RT for TNBC and provide experimental basis for the development of novel clinical treatment methods for TNBC.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: INS NPs effectively overcome many shortcomings of RT for TNBC and provide experimental basis for the development of novel clinical treatment methods for TNBC.
摘要：
背景：三阴性乳腺癌（TNBC）是预后最差的乳腺癌亚型。放射治疗（RT）是疾病的核心方式之一；然而，RT的电离辐射具有严重的副作用。RT的一贯发展方向是以较低的辐射剂量达到更好的治疗效果。研究表明，将RT与非电离辐射疗法（如光和磁疗）结合使用可以实现协同作用，从而达到减少剂量和增强疗效的目的。
方法：在本研究中，我们应用具有磁热功能的FeCoNP和光治疗剂IR-780来构建电离和非电离辐射协同纳米颗粒（INSNP）。INSNP首先进行形态学处理，尺寸,胶体稳定性，装载能力,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。在对NPs体内生物相容性进行全面评估后，建立荷瘤小鼠模型以评估其分布，有针对性的交付，和体内抗肿瘤作用。
结果：INSNP的饱和磁化强度超过72emu/g，流体动力学粒径约为40nm，带负电荷的表面，良好的胶体稳定性和包封性能。INSNP在808nm处保持IR-780的光谱特性。在激光照射下，最高温度为92°C，INSNP还实现了体内有效的热温度。体内和体外试验均证明INSNP具有良好的生物相容性。INSNP在体内注射一次后仍有效超过一周，也可以通过永磁体引导和积聚在肿瘤中。稍后，结果表明，在低剂量RT和激光照射下，联合干预组表现出显著的协同作用，ROS产生率远高于RT组和光疗组。在小鼠模型中,60%的肿瘤被完全根除。
结论：INSNPs有效地克服了RT治疗TNBC的许多缺点，为开发TNBC的新型临床治疗方法提供了实验依据。
方法：在本研究中，我们应用具有磁热功能的FeCoNP和光治疗剂IR-780来构建电离和非电离辐射协同纳米颗粒（INSNP）。INSNP首先进行形态学处理，尺寸,胶体稳定性，装载能力,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。在对NPs体内生物相容性进行全面评估后，建立荷瘤小鼠模型以评估其分布，有针对性的交付，和体内抗肿瘤作用。
结果：INSNP的饱和磁化强度超过72emu/g，流体动力学粒径约为40nm，带负电荷的表面，良好的胶体稳定性和包封性能。INSNP在808nm处保持IR-780的光谱特性。在激光照射下，最高温度为92°C，INSNP还实现了体内有效的热温度。体内和体外试验均证明INSNP具有良好的生物相容性。INSNP在体内注射一次后仍有效超过一周，也可以通过永磁体引导和积聚在肿瘤中。稍后，结果表明，在低剂量RT和激光照射下，联合干预组表现出显著的协同作用，ROS产生率远高于RT组和光疗组。在小鼠模型中,60%的肿瘤被完全根除。
结论：INSNPs有效地克服了RT治疗TNBC的许多缺点，为开发TNBC的新型临床治疗方法提供了实验依据。
