Folate-Conjugated Magnetic Nanoparticles for Tumor Hyperthermia Therapy: In Vitro and In Vivo Studies
Folate-Conjugated Magnetic Nanoparticles for Tumor Hyperthermia Therapy: In Vitro and In Vivo Studies
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用于肿瘤热疗的叶酸缀合磁性纳米颗粒：体外和体内研究
DOI：
10.1166/jnn.2016.12622
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发表时间：
2016
影响因子：
--
通讯作者：
Jintian Tang
中科院分区：
文献类型：
--
作者：
Weiping Zheng;Zhen Rong;Fuping Gao;Yuanyuan Cai;Jing Zhou;Xiaoyun Chen;Quanqiang Li;Xueyun Gao;Liang Gao;Jintian Tang
利用铁氧体纳米粒子进行磁热疗已成为治疗癌症的一种有效方法。在这项研究中，我们构建了叶酸共轭聚乙亚胺（PEI）修饰的磁性纳米颗粒（FA-PEI-MNPs），该纳米颗粒在交变磁场（AMF）中产生热量。透射电镜（TEM）显示FA-PEI-MNPs的形状接近球形。DLS法测定的纳米颗粒平均直径为30.7±7.7 nm。细胞毒实验显示FA-PEI-MNPs对L929细胞无明显的细胞毒作用。FA-PEI-MNPs对体外磁场热疗KB细胞具有良好的热疗效果，特别是在45℃和47℃时。FA-PEI-MNPs在KB细胞瘤皮下肿瘤异种移植模型中进行体内热疗，肿瘤温度升高至48℃，而体温保持在37.5℃左右。与磁场对照组相比，FA-PEI-MNPs热疗延长了生存期，66.7%（4/6）的皮下肿瘤完全消退。治疗后的组织学检查显示靠近颗粒沉积物的大面积坏死区域。这些结果表明，使用FA-PEI-MNPs进行热疗是一种有效的肿瘤特异性治疗方法。该疗法可能为其他治疗方法难治性复发性癌症提供了另一种治疗方法。
Magnetic hyperthermia using ferrite nanoparticles has emerged as a eutherapeutic approach for cancer treatment. In this study, we had constructed folate conjugated poly(ethyleneimine) (PEI) modified magnetic nanoparticles (FA-PEI-MNPs) that generate heat in an alternating magnetic field (AMF). Transmission electron microscope (TEM) showed that FA-PEI-MNPs were nearly spherical in shape. The mean diameter of these nanoparticles determined by DLS was 30.7 ± 7.7 nm. The cytotoxicity assay showed that FA-PEI-MNPs exhibited no significant cytotoxicity against L929 cells. FA-PEI-MNPs have good hyperthermia effect on KB cells In Vitro by magnetic field induced hyperthermia, especially at 45 °C and 47 °C. In In Vivo hyperthermia treatment using FA-PEI-MNPs in a subcutaneous tumor xenograft model of KB cells tumor, the tumor temperature increased to 48 °C whereas the body temperature remained at around 37.5 °C. Thermotherapy with FA-PEI-MNPs led up to prolongation of survival over magnetic field controls, 66.7% (4/6) of subcutaneous tumors regressed completely. Histological examinations after treatment revealed large necrotic areas close to particle deposits. These results suggest that hyperthermia using FA-PEI-MNPs is an effective and specific therapy for tumor. This therapy may provide an alternative way to treat recurrent cancer refractory to other modalities.