Department of Ultrasound, Peking University Third Hospital, Beijing100191, China.
Department of Ultrasound Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing100020, China.
ACS Appl Mater Interfaces. 2022 Jan 12;14(1):452-463. doi: 10.1021/acsami.1c21924. Epub 2021 Dec 27.
Trastuzumab combined with chemotherapy is the first-line treatment for advanced HER2-positive gastric cancer, but it still suffers from limited therapeutic efficiency and serious side effects, which are usually due to the poor delivery efficiency and the drug resistance of tumor cells to the chemotherapeutic drugs. Herein, a type of ultrasound microbubble for simultaneous delivery of sonosensitizers and therapeutic antibodies to achieve targeting combination of sonodynamic therapy and antibody therapy of HER2-positive gastric cancer was constructed from pyropheophorbide-lipid followed by trastuzumab conjugation (TP MBs). and studies showed that TP MBs had good biological safety, and their delivery can be monitored by ultrasound/fluorescence bimodal imaging. With ultrasound (US) located at the tumor area, TP MBs can be converted into nanoparticles (TP NPs) by US-targeted microbubble destruction; plus the enhanced permeability and retention effects and the targeting effects of trastuzumab, the enrichment of sonosensitizers and antibodies in the tumor tissue can be greatly enhanced (∼2.1 times). When combined with ultrasound, TP MBs can not only increase the uptake of sonosensitizers in HER2-positive gastric cancer NCI-N87 cells but also efficiently generate singlet oxygen to greatly increase the killing effect on cells, obviously inhibiting the tumor growth in HER2-positive gastric cancer NCI-N87 cell models with a tumor inhibition rate up to 79.3%. Overall, TP MBs combined with US provided an efficient way for co-delivery of sonosensitizers and antibodies, greatly enhancing the synergistic therapeutic effect on HER2-positive gastric cancer while effectively reducing the side effects.
曲妥珠单抗联合化疗是治疗晚期 HER2 阳性胃癌的一线治疗方法，但仍存在治疗效率有限和严重副作用的问题，这通常是由于药物递送效率差和肿瘤细胞对化疗药物的耐药性所致。在此，构建了一种由叶绿酸脂 pyropheophorbide-lipid 衍生而来的，同时用于递送声敏剂和治疗性抗体的超声微泡，以实现针对 HER2 阳性胃癌的声动力学治疗和抗体治疗的靶向联合（TP MBs）。并研究表明，TP MBs 具有良好的生物安全性，其递送可以通过超声/荧光双模成像进行监测。在肿瘤区域进行超声（US）定位后，TP MBs 可以通过 US 靶向微泡破坏转化为纳米颗粒（TP NPs）；加上曲妥珠单抗的增强渗透和保留效应和靶向作用，可以大大增强声敏剂和抗体在肿瘤组织中的富集（约 2.1 倍）。当与超声联合使用时，TP MBs 不仅可以增加 HER2 阳性胃癌 NCI-N87 细胞对声敏剂的摄取，而且还可以有效地产生单线态氧，大大提高对细胞的杀伤作用，明显抑制 HER2 阳性胃癌 NCI-N87 细胞模型中的肿瘤生长，肿瘤抑制率高达 79.3%。总的来说，TP MBs 联合 US 为声敏剂和抗体的共递供了一种高效的方法，大大增强了对 HER2 阳性胃癌的协同治疗效果，同时有效降低了副作用。
