Superparamagnetic nanoparticle clusters for cancer theranostics combining magnetic resonance imaging and hyperthermia treatment.
Superparamagnetic nanoparticle clusters for cancer theranostics combining magnetic resonance imaging and hyperthermia treatment.
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DOI：
10.7150/thno.5860
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发表时间：
2013
期刊：
影响因子：
12.4
通讯作者：
Ishimura K
中科院分区：
文献类型：
--
作者：
Hayashi K;Nakamura M;Sakamoto W;Yogo T;Miki H;Ozaki S;Abe M;Matsumoto T;Ishimura K
如果磁共振成像（MRI）和磁热疗（MHT）相结合，超顺磁性纳米粒子（SPION）可以实现癌症治疗诊断。然而，SPION的颗粒尺寸小于正常组织中有孔毛细血管的孔，因为超顺磁性仅在颗粒尺寸<10 nm时表现出来。因此，SPION从正常组织的毛细血管中渗漏，导致肿瘤中的低积累。此外，MHT研究已经以不切实际的方式进行：将磁性材料直接注射到肿瘤中和应用危险的交流（AC）磁场。为了实现MRI造影剂在肿瘤中的有效增强和MHT通过静脉注射和安全的AC磁场抑制肿瘤生长，我们聚集SPION，不仅防止它们从正常组织中的有孔毛细血管泄漏，而且增加它们的弛豫率和比吸收率。我们用叶酸（FA）和聚乙二醇（PEG）修饰簇，以促进它们在肿瘤中的积累。通过硫醇-烯点击反应同时实现了SPION簇合和FA和PEG对簇合物的修饰。静脉注射FA和PEG修饰的SPION纳米簇（FA-PEG-SPION NC）后24小时，它们在肿瘤内的癌（非坏死）组织中局部积聚，并增强了MRI对比度。此外，静脉注射NC后24 h，将小鼠置于H = 8 kA/m和f = 230 kHz（Hf = 1.8×109 A/m·s）的交流磁场中20 min。通过施加交流磁场对小鼠肿瘤进行局部加热。治疗后20 min，肿瘤的温度比周围组织高1.6 °C。治疗后35天，治疗小鼠的肿瘤体积是对照小鼠的十分之一。此外，治疗组小鼠在12周后存活;对照组小鼠在治疗后8周死亡。
Superparamagnetic nanoparticles (SPIONs) could enable cancer theranostics if magnetic resonance imaging (MRI) and magnetic hyperthermia treatment (MHT) were combined. However, the particle size of SPIONs is smaller than the pores of fenestrated capillaries in normal tissues because superparamagnetism is expressed only at a particle size <10 nm. Therefore, SPIONs leak from the capillaries of normal tissues, resulting in low accumulation in tumors. Furthermore, MHT studies have been conducted in an impractical way: direct injection of magnetic materials into tumor and application of hazardous alternating current (AC) magnetic fields. To accomplish effective enhancement of MRI contrast agents in tumors and inhibition of tumor growth by MHT with intravenous injection and a safe AC magnetic field, we clustered SPIONs not only to prevent their leakage from fenestrated capillaries in normal tissues, but also for increasing their relaxivity and the specific absorption rate. We modified the clusters with folic acid (FA) and polyethylene glycol (PEG) to promote their accumulation in tumors. SPION clustering and cluster modification with FA and PEG were achieved simultaneously via the thiol-ene click reaction. Twenty-four hours after intravenous injection of FA- and PEG-modified SPION nanoclusters (FA-PEG-SPION NCs), they accumulated locally in cancer (not necrotic) tissues within the tumor and enhanced the MRI contrast. Furthermore, 24 h after intravenous injection of the NCs, the mice were placed in an AC magnetic field with H = 8 kA/m and f = 230 kHz (Hf = 1.8×109 A/m∙s) for 20 min. The tumors of the mice underwent local heating by application of an AC magnetic field. The temperature of the tumor was higher than the surrounding tissues by ≈6°C at 20 min after treatment. Thirty-five days after treatment, the tumor volume of treated mice was one-tenth that of the control mice. Furthermore, the treated mice were alive after 12 weeks; control mice died up to 8 weeks after treatment.
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影响因子：
15
作者：
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通讯作者：
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影响因子：
38.3
作者：
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影响因子：
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