Feng Ziyan, Yao Yongchao, Wang Ziyao, Xiang Xi, Wang Liyun, Xiao Xueyang, Tang Yuanjiao, Hu Wenchuang, Qiu Li, Qian Zhiyong
Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China; Department of Ultrasound, West China Hospital, Sichuan University, Chengdu, 610041, China.
Precision Medicine Translational Research Center (PMTRC), West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
Biomaterials. 2026 Jan;324:123450. doi: 10.1016/j.biomaterials.2025.123450. Epub 2025 May 30.
Sonodynamic therapy (SDT) offers a new, non-invasive therapeutic choice for melanoma. However, direct use of sonosensitizer like chlorin e6 (Ce6) may face problems like poor drug solubility and off-target effects. Besides, using SDT alone may be deficient to treat melanoma. Nanobubbles (NBs) are novel extravascular ultrasound contrast agents with the ability to perform ultrasound-triggered drug delivery. On the other hand, we found that cell membrane disruption therapy is suitable for working synergistically with SDT. In this study, we used quaternary ammonium salts (QAS) to prepare NBs with therapeutic effect. Besides delivering Ce6, QAS NBs can destroy tumor cell membranes using its special structure, thus enhancing the effect of SDT. The resulting Ce6@QAS NBs had excellent ultrasound-triggered imaging effects and photoacoustic (PA) imaging effects both in vivo and in vitro. The effect in killing tumor cells has been confirmed, including the performance to destroy cells by their outer QAS shells, and the generation of reactive oxygen species (ROS) in SDT process. We found that treated tumor cells were induced to undergo immunogenic cell death (ICD). In the Ce6@QAS NBs with ultrasound group, the tumor growth was significantly inhibited, and anti-tumor immunity was activated. These results suggest that Ce6@QAS NBs can achieve physicochemical synergistic antitumor therapy while performing multimodal imaging.
声动力疗法（SDT）为黑色素瘤提供了一种新的非侵入性治疗选择。然而，直接使用诸如氯e6（Ce6）之类的声敏剂可能会面临药物溶解度差和脱靶效应等问题。此外，单独使用SDT治疗黑色素瘤可能存在不足。纳米气泡（NBs）是新型的血管外超声造影剂，具有执行超声触发药物递送的能力。另一方面，我们发现细胞膜破坏疗法适合与SDT协同作用。在本研究中，我们使用季铵盐（QAS）制备具有治疗效果的NBs。除了递送Ce6外，QAS NBs还可以利用其特殊结构破坏肿瘤细胞膜，从而增强SDT的效果。所得的Ce6@QAS NBs在体内和体外均具有出色的超声触发成像效果和光声（PA）成像效果。其杀伤肿瘤细胞的效果已得到证实，包括其外层QAS壳破坏细胞的性能以及SDT过程中活性氧（ROS）的产生。我们发现经处理的肿瘤细胞被诱导发生免疫原性细胞死亡（ICD）。在超声处理的Ce6@QAS NBs组中，肿瘤生长受到显著抑制，抗肿瘤免疫被激活。这些结果表明，Ce6@QAS NBs在进行多模态成像的同时可以实现物理化学协同抗肿瘤治疗。
