Hyperthermia treatment of tumors by mesenchymal stem cell-delivered superparamagnetic iron oxide nanoparticles.
Hyperthermia treatment of tumors by mesenchymal stem cell-delivered superparamagnetic iron oxide nanoparticles.
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DOI：
10.2147/ijn.s94255
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发表时间：
2016
影响因子：
8
通讯作者：
Janes SM
中科院分区：
文献类型：
--
作者：
Kalber TL;Ordidge KL;Southern P;Loebinger MR;Kyrtatos PG;Pankhurst QA;Lythgoe MF;Janes SM
磁热疗是一种潜在的癌症治疗方法，利用超顺磁性氧化铁纳米粒子（SPIONs）对交变磁场（AMF）产生共振反应，从而产生热量。我们之前的研究表明，间充质干细胞（MSCs）可以用SPIONs标记，对细胞增殖或存活没有影响，并且在全身给药一小时内，它们在体内迁移并整合到肿瘤中。在这里，我们报告了磁性标记的人间充质干细胞在免疫受损小鼠模型中的一些长期（长达3周）整合后的特征。我们初步评估了SPIONs的大小和涂层如何决定MSCs的负载能力和细胞加热。Ferucarbotran®是这些测试中最好的，具有最好的同类加热能力，并且是唯一一个在细胞内化后保留这种能力的。通过皮下侧腹注射50万个载ferucarbotrans的MSCs和100万个OVCAR-3卵巢肿瘤细胞，建立小鼠模型。2周后，肿瘤体积达到~100µL，第三周进入快速生长阶段，达到~300µL。在未接受AMF治疗的对照小鼠中，磁共振成像（MRI）数据显示，标记的MSCs在整个3周的时间内都被纳入肿瘤并保留在肿瘤内。在amf处理的小鼠中，第一次应用时观察到温度升高~4°C，之后MRI显示负对比丢失，表明MSCs已经死亡并从肿瘤中清除。这种amf后细胞的去除是通过组织学检查和随后的磁热效应水平降低来证实的。尽管有证据表明，在装载spion的MSCs中存在amf引发的反应，并且与之前关于免疫功能小鼠模型中肿瘤缓解的报道相反，在这种情况下，在总体肿瘤大小或生长特征方面没有测量到显着差异。我们讨论了这些结果对肿瘤热疗临床传递的影响，以及首选治疗途径可能涉及AMF作为自体免疫反应的辅助剂的可能性。
Magnetic hyperthermia – a potential cancer treatment in which superparamagnetic iron oxide nanoparticles (SPIONs) are made to resonantly respond to an alternating magnetic field (AMF) and thereby produce heat – is of significant current interest. We have previously shown that mesenchymal stem cells (MSCs) can be labeled with SPIONs with no effect on cell proliferation or survival and that within an hour of systemic administration, they migrate to and integrate into tumors in vivo. Here, we report on some longer term (up to 3 weeks) post-integration characteristics of magnetically labeled human MSCs in an immunocompromized mouse model. We initially assessed how the size and coating of SPIONs dictated the loading capacity and cellular heating of MSCs. Ferucarbotran® was the best of those tested, having the best like-for-like heating capability and being the only one to retain that capability after cell internalization. A mouse model was created by subcutaneous flank injection of a combination of 0.5 million Ferucarbotran-loaded MSCs and 1.0 million OVCAR-3 ovarian tumor cells. After 2 weeks, the tumors reached ~100 µL in volume and then entered a rapid growth phase over the third week to reach ~300 µL. In the control mice that received no AMF treatment, magnetic resonance imaging (MRI) data showed that the labeled MSCs were both incorporated into and retained within the tumors over the entire 3-week period. In the AMF-treated mice, heat increases of ~4°C were observed during the first application, after which MRI indicated a loss of negative contrast, suggesting that the MSCs had died and been cleared from the tumor. This post-AMF removal of cells was confirmed by histological examination and also by a reduced level of subsequent magnetic heating effect. Despite this evidence for an AMF-elicited response in the SPION-loaded MSCs, and in contrast to previous reports on tumor remission in immunocompetent mouse models, in this case, no significant differences were measured regarding the overall tumor size or growth characteristics. We discuss the implications of these results on the clinical delivery of hyperthermia therapy to tumors and on the possibility that a preferred therapeutic route may involve AMF as an adjuvant to an autologous immune response.