Stem cell-based gene therapy activated using magnetic hyperthermia to enhance the treatment of cancer.
Stem cell-based gene therapy activated using magnetic hyperthermia to enhance the treatment of cancer.
复制标题
使用磁热疗激活基于干细胞的基因疗法，以增强癌症治疗。
DOI：
10.1016/j.biomaterials.2015.11.023
复制
发表时间：
2016-03
期刊：
影响因子：
14
通讯作者：
Lee KB
中科院分区：
文献类型：
--
作者：
Yin PT;Shah S;Pasquale NJ;Garbuzenko OB;Minko T;Lee KB
以干细胞为基础的基因疗法，其中干细胞经过基因工程以表达治疗分子，由于其天生的肿瘤归宿能力，已显示出巨大的癌症应用潜力。然而，传统的基于干细胞的基因治疗由于我们目前无法控制治疗基因实际上何时被打开而受到阻碍，从而导致了有害的副作用。在这里，我们报道了磁性核壳纳米颗粒在脂肪来源的间充质干细胞(AD-MSCs)中的双重应用，即传递和激活编码肿瘤坏死因子相关的凋亡诱导配体(TRAIL)的热诱导基因载体。通过将AD-MSCs的肿瘤趋向性与基于MCNP的时空递送和TRAIL表达的激活相结合，该平台提供了一种有吸引力的手段来加强我们对基于干细胞的基因治疗的激活的控制。特别是，我们发现这些工程化的AD-MSCs保留了它们天生的增殖、分化能力，最重要的是，它们是肿瘤的家园，使它们成为理想的细胞载体。此外，工程化AD-MSCs暴露于弱磁加热后，可选择性表达AD-MSCs中的TRAIL，从而在体内外诱导卵巢癌细胞显著死亡。
Stem cell-based gene therapies, wherein stem cells are genetically engineered to express therapeutic molecules, have shown tremendous potential for cancer applications owing to their innate ability to home to tumors. However, traditional stem cell-based gene therapies are hampered by our current inability to control when the therapeutic genes are actually turned on, thereby resulting in detrimental side effects. Here, we report the novel application of magnetic core-shell nanoparticles for the dual purpose of delivering and activating a heat-inducible gene vector that encodes TNF-related apoptosis-inducing ligand (TRAIL) in adipose-derived mesenchymal stem cells (AD-MSCs). By combining the tumor tropism of the AD-MSCs with the spatiotemporal MCNP-based delivery and activation of TRAIL expression, this platform provides an attractive means with which to enhance our control over the activation of stem cell-based gene therapies. In particular, we found that these engineered AD-MSCs retained their innate ability to proliferate, differentiate, and, most importantly, home to tumors, making them ideal cellular carriers. Moreover, exposure of the engineered AD-MSCS to mild magnetic hyperthermia resulted in the selective expression of TRAIL from the engineered AD-MSCs and, as a result, induced significant ovarian cancer cell death in vitro and in vivo.