The Research and Application Center of Precision Medicine, The Second Affiliated Hospital, Zhengzhou University, Zhengzhou, PR China; Department of Breast Surgery, Guangxi Medical University Cancer Hospital, Nanning, 530000, China; Guangxi Clinical Research Center for Anesthesiology, Nanning, 530000, China.
School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, China; Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction and Institute for Advanced Study, The Hong Kong University of Science and Technology Clear Water Bay, Kowloon, Hong Kong, 999077, China.
Biomaterials. 2023 Apr;295:122034. doi: 10.1016/j.biomaterials.2023.122034. Epub 2023 Feb 1.
Radioresistance of Cancer stem cell (CSC) is an important cause of tumor recurrence after radiotherapy (RT). Herein, we designed a type I aggregation-induced emission (AIE) photosensitiser-loaded biomimetic mesoporous organosilicon nanosystem (PMT) for precise depletion of CSC to prevent tumor recurrence after RT. This PMT system is composed of a type I AIE photosensitiser (TBP-2) loaded mesoporous organosilicon nanoparticles (MON) with an outer platelet membrane. The PMT system is able to specifically target CSC. Intracellular glutathione activity leads to MON degradation and the release of TBP-2. Type I photodynamic therapy is activated by exposure to white light, producing a large amount of hydroxyl radicals to promote CSC death. The results of in vivo experiments demonstrated specific removal of CSC following PMT treatment, with no tumor recurrence observed when combined with RT. However, tumor recurrence was observed in mice that received RT only. The expression of CSC markers was significantly reduced following PMT treatment. We demonstrate the development of a system for the precise removal of CSC with good biosafety and high potential for clinical translation. We believe the PMT nanosystem represents a novel idea in the prevention of tumor recurrence.
癌症干细胞（CSC）的放射抵抗性是放疗（RT）后肿瘤复发的一个重要原因。在此，我们设计了一种 I 型聚集诱导发射（AIE）光敏剂负载仿生介孔有机硅纳米系统（PMT），用于精确耗尽 CSC，以防止 RT 后肿瘤复发。该 PMT 系统由负载介孔有机硅纳米粒子（MON）的 I 型 AIE 光敏剂（TBP-2）组成，其外表面有血小板膜。PMT 系统能够特异性靶向 CSC。细胞内谷胱甘肽活性导致 MON 降解和 TBP-2 的释放。I 型光动力疗法在暴露于白光下被激活，产生大量的羟基自由基，促进 CSC 死亡。体内实验结果表明，PMT 治疗后 CSC 被特异性去除，与 RT 联合治疗时未见肿瘤复发，但仅接受 RT 的小鼠则观察到肿瘤复发。PMT 治疗后 CSC 标志物的表达明显降低。我们证明了一种具有良好生物安全性和高临床转化潜力的精确去除 CSC 的系统的发展。我们相信，PMT 纳米系统代表了预防肿瘤复发的一种新思想。
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