Magnetic drug targeting reduces the chemotherapeutic burden on circulating leukocytes.

Magnetic drug targeting reduces the chemotherapeutic burden on circulating leukocytes.
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DOI:
10.3390/ijms14047341
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发表时间:
2013-04-02
影响因子:
5.6
通讯作者:
Alexiou C
Alexiou C
中科院分区:
生物学2区
文献类型:
--
作者:
Janko C;Dürr S;Munoz LE;Lyer S;Chaurio R;Tietze R;Löhneysen Sv;Schorn C;Herrmann M;Alexiou C

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磁性药物靶向(MDT)在细胞毒性药物治疗期间改善健康组织和细胞的完整性。抗癌药物与超顺磁性氧化铁纳米颗粒(SPION)结合,注射到肿瘤的血管供应中,并通过外部磁场直接进入肿瘤。在这项研究中,我们研究了SPION,米托蒽醌(MTO)和SPIONMTO对体外细胞活力和体内循环白细胞非特异性摄取MTO的影响。MDT与常规化疗进行比较。在Jurkat细胞培养物中通过流式细胞术评估MTO摄取和对细胞活力的影响。为了分析体内循环白细胞的MTO负荷,我们用MDT和常规化疗治疗荷瘤兔。体外实验显示剂量依赖性MTO摄取和Jurkat细胞活力和增殖的降低。MTO和SPIONMTO显示出相似的细胞毒活性。在测试浓度下,未加载的SPION对细胞活力没有任何影响。与体内全身给药相比,采用SPIONMTO的MDT显著降低了循环白细胞中的化疗负荷。我们证明,与常规化疗相比,MDT可以保护免疫系统。
Magnetic drug targeting (MDT) improves the integrity of healthy tissues and cells during treatment with cytotoxic drugs. An anticancer drug is bound to superparamagnetic iron oxide nanoparticles (SPION), injected into the vascular supply of the tumor and directed into the tumor by means of an external magnetic field. In this study, we investigated the impact of SPION, mitoxantrone (MTO) and SPIONMTO on cell viability in vitro and the nonspecific uptake of MTO into circulating leukocytes in vivo. MDT was compared with conventional chemotherapy. MTO uptake and the impact on cell viability were assessed by flow cytometry in a Jurkat cell culture. In order to analyze MTO loading of circulating leukocytes in vivo, we treated tumor-bearing rabbits with MDT and conventional chemotherapy. In vitro experiments showed a dose-dependent MTO uptake and reduction in the viability and proliferation of Jurkat cells. MTO and SPIONMTO showed similar cytotoxic activity. Non-loaded SPION did not have any effect on cell viability in the concentrations tested. Compared with systemic administration in vivo, MDT employing SPIONMTO significantly decreased the chemotherapeutic load in circulating leukocytes. We demonstrated that MDT spares the immune system in comparison with conventional chemotherapy.
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