磁感应热疗新技术协同治疗B细胞淋巴瘤的可行性研究

This project is to develop a new treatment strategy to deal with recurrent B-cell non-hodgkin lymphoma. Magnetic-mediated hyperthermia (MMH) was a technology based on the fact that micro/nano particles could be heated in an alternating magnetic field. The heated particles, coupled with specific targeting antibodies, which were able to focus on the tumor, could then sensitized the local anticancer agents or kill the tumor cells directly. Our team has been devoted to MMH research for more than a decade, which involved screening micro/nano granules for MMH, establishing the combination of micro/nano particles with antibody molecules, and developing MMH apparatus as well as its security and efficacy by studies in vitro and in vivo. What’s more, the clinical trials of applying MMH in cancer therapy have also been conducted, which indicated the leading role of our research nationally in this field. This study involves developing electromagnetic simulation of magnetic induction device with coil structure as well as establishing magnetic-mediated micro/nano granular medium heating models, searching for efficient magnetic micro/nano materials and coupling target antibody such as rituximab. Thus the project aims to explore the safety and efficacy of using MMH in lymphoma treatment through animal experiments, along with the possible mechanisms of MMH in drug sensitization. This is the first exploration of combining magnetic micro/nano particles with target antibodies to lymphoma and using MMH in lymphoma treatment, which will contribute to new physical therapy for B-cell non-hodgkin lymphoma.

应对非霍奇金B细胞淋巴瘤的复发需要研发新的治疗技术。磁感应热疗新技术是以磁性微纳介质为基体耦联特异性靶向抗体，与肿瘤细胞特异性靶点结合，在交变磁场作用下磁性介质感应升温实现靶向热疗，达到杀灭或增敏药物目的。我们团队经过十多年长期研究，筛选了微米和纳米多种介质，确立了介质与蛋白质结合技术，研制了交变磁场发生设备，并通过对脑胶质瘤、肝癌、乳腺癌等细胞和动物实验证明安全和有效；继德日美之后，我们已将磁感应热疗技术推向临床试验，确立技术领先地位。我们拟通过微纳介质磁热效应建模及电磁场仿真，完善线圈式实验设备研制；筛选高效升温磁性微纳材料，耦联利妥昔等靶向抗体；并通过人淋巴瘤细胞和动物肿瘤模型明确其安全性和有效性，探索该技术增敏药物的可能性与机理。本课题是国内外首次探索微纳磁性介质与淋巴瘤靶向抗体结合，将磁感应热疗新技术应用于淋巴瘤治疗可能性，为我国创新发展淋巴瘤物理治疗新技术提供新线索。

应对非霍奇金B细胞淋巴瘤的复发需要研发新的治疗技术。磁感应热疗新技术是以磁性微纳介质为基体耦联特异性靶向抗体，与肿瘤细胞特异性靶点结合，在交变磁场作用下磁性介质感应升温实现靶向热疗，达到杀灭或增敏药物目的。我们团队经过十多年长期研究，筛选了微米和纳米多种介质，确立了介质与蛋白质结合技术，研制了交变磁场发生设备，并通过对脑胶质瘤、肝癌、乳腺癌等细胞和动物实验证明安全和有效；继德日美之后，我们已将磁感应热疗技术推向临床试验，确立技术领先地位。在线圈式磁感应肿瘤治疗设备设计中,为了提高治疗磁场的强度与均匀度,需要对传统的圆形同轴线圈进行改进。从线圈的工作原理进行分析,结合实际应用场合与磁场改善的需求,改进了传统的圆形同轴线圈,采用了D形线圈设计。通过软件仿真,在相同条件下D形线圈与圆形线圈相比,其中心磁场强度提高了约5.9%,有效治疗空间增加了约4.6%,设备性能有了一定的提高。线圈电感值的仿真与实际测量结果均符合设备要求。筛选高效升温磁性材料不锈钢空心球具有良好的发热效率以及细胞相容性，磁感应热疗磁性介质应用于淋巴瘤治疗在细胞水平是可行的。磁感应热疗联合艾迪注射液以及利妥昔单抗，可增强对淋巴瘤细胞株Daudi的增殖抑制作用并促使细胞的凋亡，效果与单独使用艾迪注射液或者利妥昔单抗治疗有明显差异，表明磁感应热疗对艾迪注射液以及利妥昔单抗注射液有协同增敏的效果，为我国创新发展淋巴瘤物理治疗新技术提供新线索。诱导细胞凋亡和细胞周期阻滞可能是磁感应热疗抑制肿瘤生长的机制之一，其他的作用机制尚需进一步深入探讨。