International Institute of Nano and Molecular Medicine, University of Missouri, Columbia, United States of America.
Bond Life Science Center, University of Missouri, Columbia, United States of America.
PLoS One. 2019 Sep 3;14(9):e0222022. doi: 10.1371/journal.pone.0222022. eCollection 2019.
In the United States, breast cancer is one of the most common and the second leading cause of cancer-related death in women. Treatment modalities for mammary tumor are surgical removal of the tumor tissue followed by either chemotherapy or radiotherapy or both. Radiation therapy is a whole body irradiation regimen that suppresses the immune system leaving hosts susceptible to infection or secondary tumors. Boron neutron capture therapy (BNCT) in that regard is more selective, the cells that are mostly affected are those that are loaded with 109 or more 10B atoms. Previously, we have described that liposomal encapsulation of boron-rich compounds such as TAC and MAC deliver a high payload to the tumor tissue when injected intravenously. Here we report that liposome-mediated boron delivery to the tumor is inversely proportional to the size of the murine mammary (EMT-6) tumors. The plausible reason for the inverse ratio of boron and EMT-6 tumor size is the necrosis in these tumors, which is more prominent in the large tumors. The large tumors also have receding blood vessels contributing further to poor boron delivery to these tumors. We next report that the presence of boron in blood is essential for the effects of BNCT on EMT-6 tumor inhibition as direct injection of boron-rich liposomes did not provide any added advantage in inhibition of EMT-6 tumor in BALB/c mice following irradiation despite having a significantly higher amount of boron in the tumor tissue. BNCT reaction in PBMCs resulted in the modification of these cells to anti-tumor phenotype. In this study, we report the immunomodulatory effects of BNCT when boron-rich compounds are delivered systemically.
在美国，乳腺癌是女性最常见的癌症之一，也是癌症相关死亡的第二大原因。乳腺肿瘤的治疗方法是手术切除肿瘤组织，然后进行化疗或放疗，或两者同时进行。放射治疗是一种全身照射方案，会抑制免疫系统，使宿主易感染或发生继发性肿瘤。硼中子俘获治疗（BNCT）在这方面更具选择性，受影响最大的细胞是那些负载 109 个或更多 10B 原子的细胞。此前，我们已经描述了将富含硼的化合物（如 TAC 和 MAC）包封在脂质体中，当静脉注射时，这些化合物可以向肿瘤组织提供高载药量。在这里，我们报告说，脂质体介导的硼向肿瘤的输送与小鼠乳腺（EMT-6）肿瘤的大小成反比。硼与 EMT-6 肿瘤大小成反比的原因可能是这些肿瘤发生了坏死，在较大的肿瘤中更为明显。较大的肿瘤也有退缩的血管，进一步导致这些肿瘤的硼输送不良。我们接下来报告说，硼在血液中的存在对于 BNCT 对 EMT-6 肿瘤抑制的影响是必不可少的，因为尽管在肿瘤组织中硼的含量明显更高，但直接注射富含硼的脂质体并没有为抑制 BALB/c 小鼠的 EMT-6 肿瘤提供任何额外的优势。BNCT 在 PBMCs 中的反应导致这些细胞向抗肿瘤表型的修饰。在这项研究中，我们报告了硼化合物系统给药时 BNCT 的免疫调节作用。
