College of Materials Science & Engineering, Sichuan University, Chengdu 610065, China.
Biomater Sci. 2018 May 29;6(6):1535-1545. doi: 10.1039/c8bm00142a.
Although microwave (MW) thermal therapy has been widely studied for the treatment of tumors due to its less invasiveness, recurrence of tumors is still observed because of the relatively low bioavailability of MW sensitizers. For enhancing the bioavailability of MW sensitizers, triphenyl phosphate (TPP)-conjugated and doxorubicin (DOX)-loaded porous zirconium metal-organic framework nanocubes (ZrMOF NCs) modified with polyethylene glycol (PEG), ZrMOF-PEG-TPP@DOX NCs, were prepared as a MW sensitizer with mitochondrial-targeting ability. Moreover, the mitochondria are more susceptible to heat than the tumor tissues; this leads to improved tumor cell apoptosis. The results of this study indicate that ZrMOF NCs exhibit excellent heating effects due to the increased collisions of ions in the micropores of ZrMOFs under MW irradiation. In addition, ZrMOF-PEG-TPP@DOX NCs show preferential aggregation in the mitochondria, confirmed by confocal microscopy images. In vivo MW thermal therapeutic efficacy of ZrMOF-PEG-TPP@DOX NCs + MW is also better without recurrence during treatment than that of ZrMOF-PEG@DOX NCs + MW at a similar thermal therapeutic temperature; this reveals that the mitochondrial-targeting strategy can enhance the MW thermal therapeutic efficacy. This study provides a new biosafe MW sensitizer with mitochondrial-targeting ability for enhancing the efficacy of MW thermal therapy against tumors.
虽然微波（MW）热疗因其侵袭性较小而被广泛研究用于治疗肿瘤，但由于 MW 敏化剂的生物利用度相对较低，肿瘤仍会复发。为了提高 MW 敏化剂的生物利用度，将三苯基膦（TPP）偶联和阿霉素（DOX）负载的聚乙二醇（PEG）修饰的多孔锆金属-有机骨架纳米立方体（ZrMOF NCs）制备成具有线粒体靶向能力的 MW 敏化剂。此外，线粒体比肿瘤组织更容易受到热的影响，这导致肿瘤细胞凋亡增加。本研究结果表明，由于 MW 照射下 ZrMOFs 微孔中离子的增加碰撞，ZrMOF NCs 表现出优异的加热效果。此外，通过共聚焦显微镜图像证实，ZrMOF-PEG-TPP@DOX NCs 优先聚集在线粒体中。在体内 MW 热疗疗效方面，ZrMOF-PEG-TPP@DOX NCs+MW 也优于在相似热疗温度下的 ZrMOF-PEG@DOX NCs+MW，没有复发；这表明线粒体靶向策略可以增强 MW 热疗的疗效。本研究为增强 MW 热疗对肿瘤的疗效提供了一种具有线粒体靶向能力的新型生物安全 MW 敏化剂。
