曲妥珠单抗
微气泡
体内
声动力疗法
癌症研究
癌症
医学
药物输送
癌细胞
抗体
超声波
乳腺癌
药理学
材料科学
纳米技术
内科学
免疫学
生物
生物技术
放射科
作者
Lihong Sun,Jinxia Zhang,Menghong Xu,Lulu Zhang,Qinglian Tang,Jing Chen,Ming Gong,Shijie Sun,Huiyu Ge,Shumin Wang,Xiaolong Liang,Ligang Cui
标识
DOI:10.1021/acsami.1c21924
摘要
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). In vitro and in vivo studies showed that TP MBs had good biological safety, and their in vivo 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) in situ 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.
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