Real-Time Imaging Tracking of Engineered Macrophages as Ultrasound-Triggered Cell Bombs for Cancer Treatment
Real-Time Imaging Tracking of Engineered Macrophages as Ultrasound-Triggered Cell Bombs for Cancer Treatment
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工程化巨噬细胞的实时成像跟踪作为超声波触发的细胞炸弹用于癌症治疗
DOI：
10.1002/adfm.201910304
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发表时间：
2020
影响因子：
19
通讯作者：
Yan Fei
中科院分区：
文献类型：
--
作者：
Xu Zhili;Liu Hongmei;Tian Hao;Yan Fei
基于细胞的药物传递系统由于其高载药能力和固有的肿瘤归巢能力，是一个很有前途的肿瘤靶向治疗平台。然而，这些载体细胞的实时跟踪和胶囊药物的控制释放仍然具有挑战性。本研究通过将多柔比星（DOX）和相变全氟戊烷（PFP）包封到中空的介孔有机二氧化硅纳米颗粒（HMONs）中，制备装载DOX/PFP的HMONs (DPH)，然后内化到巨噬细胞（RAW 264.7细胞），从而开发出可超声激活的细胞炸弹。由此产生的细胞炸弹（DPH‐RAWs）可以维持肿瘤的生存能力并主动返回肿瘤。特别是，由于在37°C的细胞孵育过程中，一小部分PFP会汽化，因此可以使用超声波实时跟踪它们的迁移。在肿瘤部位积累后，剩余的PFP可以通过短脉冲高强度聚焦超声（HIFU）超声触发进一步汽化，导致产生几个大微泡，破坏DPH - RAWs并允许药物从这些细胞中释放出来。DPH - RAWs联合短脉冲HIFU超声可显著抑制肿瘤生长，延长荷瘤小鼠的生存期。总之，这项研究为基于细胞的药物传递系统提供了一种新的方法，用于实时跟踪它们的迁移和靶向癌症治疗。
Cell‐based drug delivery systems are a promising platform for tumor‐targeted therapy due to their high drug‐loading capacities and inherent tumor‐homing abilities. However, the real‐time tracking of these carrier cells and controlled release of the encapsulated drugs are still challenging. Here, ultrasound‐activatable cell bombs are developed by encapsulating doxorubicin (DOX) and phase transformable perfluoropentane (PFP) into hollow mesoporous organosilica nanoparticles (HMONs) to prepare DOX/PFP‐loaded HMONs (DPH), followed by internalization into macrophages (RAW 264.7 cells). The resulting cell bombs (DPH‐RAWs) can maintain viability and actively home to the tumor. Especially, their migration can be tracked in real time using ultrasound due to the vaporization of a small portion of PFP during cell incubation at 37 °C. After accumulation at the tumor site, the further vaporization of remaining PFP can be triggered by a short‐pulsed high intensity focused ultrasound (HIFU) sonication, resulting in the generation of several large microbubbles, which destroys DPH‐RAWs and allows drug release out of these cells. The DPH‐RAWs combined with short‐pulsed HIFU sonication significantly inhibit tumor growth and prolong survival of tumor‐bearing mice. In conclusion, this study provides a new approach to cell‐based drug delivery systems for real‐time tracking of their migration and targeted cancer treatment.