Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-Professorship, Universitätsklinikum Erlangen, Erlangen, Germany.
Department of Chemistry and Pharmacy, Division of Pharmaceutics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Int J Nanomedicine. 2019 Oct 24;14:8421-8432. doi: 10.2147/IJN.S218488. eCollection 2019.
PURPOSE: Immune activation with T cell tumor infiltration is beneficial for the prognosis of patients suffering from solid cancer. Depending on their immune status, solid tumors can be immunologically classified into three groups: "hot" tumors are infiltrated with T lymphocytes, "cold" tumors are not infiltrated and "immune excluded" tumors are only infiltrated in the peripheral tumor tissue. Checkpoint inhibitors provide new therapeutic options for "hot" tumors by triggering the immune response of T cells. In order to enable this for cold tumors as well, T cells must be enriched in the tumor. Therefore, we use the principle of magnetic targeting to guide T cells loaded with citrate-coated superparamagnetic iron oxide nanoparticles (SPION) to the tumor by an externally applied magnetic field. METHODS: SPION were produced by alkaline coprecipitation of iron(II) and iron(III) chloride and in situ coating with sodium citrate. The concentration-dependent cytocompatibility of the particles was determined by flow cytometry and blood stability assays. Atomic emission spectroscopy was used for the quantification of the particle uptake into T lymphocytes. The attractability of the loaded cells was observed by live-cell imaging in the presence of an externally applied magnetic field. RESULTS: SPION displayed good cytocompatibility to T cells and did not show any sign of aggregation in blood. Finally, SPION-loaded T cells were strongly attracted by a small external magnet. CONCLUSION: T cells can be "magnetized" by incorporation of SPION for magnetic targeting. The production of the particle-cell hybrid system is straightforward, as the loading process only requires basic laboratory devices and the loading efficiency is sufficient for cells being magnetically controllable. For these reasons, SPION are potential suitable candidates for magnetic T cell targeting.
目的:T 细胞肿瘤浸润引起的免疫激活对患有实体瘤的患者的预后有益。根据其免疫状态,实体瘤可分为三类:“热”肿瘤浸润 T 淋巴细胞,“冷”肿瘤未浸润,“免疫排除”肿瘤仅浸润肿瘤外周组织。通过触发 T 细胞免疫反应,检查点抑制剂为“热”肿瘤提供了新的治疗选择。为了使“冷”肿瘤也能做到这一点,必须在肿瘤中富集 T 细胞。因此,我们利用磁靶向原理,通过外部施加的磁场将负载柠檬酸的超顺磁性氧化铁纳米粒子(SPION)的 T 细胞引导至肿瘤。
方法:通过铁(II)和铁(III)氯化物的碱性共沉淀和原位用柠檬酸钠进行包覆,制备 SPION。通过流式细胞术和血液稳定性测定来确定颗粒的浓度依赖性细胞相容性。原子发射光谱法用于定量测定颗粒摄取到 T 淋巴细胞中。通过在存在外部磁场的情况下进行活细胞成像来观察负载细胞的吸引力。
结果:SPION 对 T 细胞具有良好的细胞相容性,在血液中没有任何聚集的迹象。最后,负载 SPION 的 T 细胞被一个小的外部磁铁强烈吸引。
结论:通过掺入 SPION 可以对 T 细胞进行“磁化”,以进行磁靶向。该颗粒-细胞杂交系统的制备过程简单,因为负载过程仅需要基本的实验室设备,并且负载效率足以使细胞能够进行磁性控制。基于这些原因,SPION 可能是磁性 T 细胞靶向的潜在合适候选物。
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