Ultrasound-Augmented Phase Transition Nanobubbles for Targeted Treatment of Paclitaxel-Resistant Cancer
Ultrasound-Augmented Phase Transition Nanobubbles for Targeted Treatment of Paclitaxel-Resistant Cancer
复制标题
超声增强相变纳米气泡用于紫杉醇耐药癌症的靶向治疗
DOI：
10.1021/acs.bioconjchem.0c00364
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发表时间：
2020
影响因子：
4.7
通讯作者：
Qiu Li
中科院分区：
文献类型：
--
作者：
Zhu Yi;Zhang Guonan;Li Meiying;Ma Lang;Huang Jianming;Qiu Li
大多数上皮性卵巢癌（EOCs）的紫杉醇（PTX）耐药是由toll样受体-髓样分化因子2/髓样分化因子88 （TLR4-MD2/MyD88）信号通路介导的，其粘膜蛋白16 （MUC16）表达增加。6-Shogaol （6S）是一种具有亲脂性的α、β-不饱和羰基化合物，可以阻断ptx诱导的激活MyD88/NF-κB信号通路的TLR4-MD2复合物的形成。为了提高6S的有效性，增强PTX的敏感性，增强PTX耐药癌症治疗的靶向能力，我们报道了一类负载6S的相变纳米泡与MUC16抗体偶联（6S@NBs-MUC16A），通过超声控制的靶向递送6S，可以增强PTX对EOC细胞的敏感性。6S@NB-MUC16A可提高6S在MyD88+EOC区域的靶向效率和组织分布，1 MHz超声可作为引发剂触发纳米气泡“爆炸”，促进6S释放。此外，体内评估结果表明，与单独使用PTX的对照组相比，超声增强6S@NB-MUC16A可显著提高EOC对PTX的反应和肿瘤生长的抑制率，并且对关键器官的毒性更小。超声增强6S@NB-MUC16A具有较低的细胞毒性，可以作为一种潜在的纳米系统来克服EOC中PTX的耐药性，这为其在生物领域的应用提供了潜在的可能性。
Paclitaxel (PTX) resistance in most epithelial ovarian cancers (EOCs) with increasing membrane expression of mucin 16 (MUC16) is mediated by the Toll-like receptor-myeloid differentiation factor 2/myeloid differentiation factor 88 (TLR4-MD2/MyD88) signaling pathway. 6-Shogaol (6S), an α,β-unsaturated carbonyl compound with lipophilic property, can block PTX-induced formation of the TLR4-MD2 complex that activates the MyD88/NF-κB signaling pathway. Herein, to improve the effectiveness of 6S, augment the sensibility of PTX, and enhance the targeting ability of PTX-resistant cancer therapies, we report a class of 6S-loaded phase transition nanobubbles conjugated with the MUC16 antibody (6S@NBs-MUC16A), which can enhance the sensitivity of PTX to EOC cells through ultrasound-controlled targeted-delivery of 6S. The 6S@NB-MUC16A could enhance the targeting efficiency and organizational distribution of 6S in MyD88+EOC area, and the 1 MHz ultrasound can be used as an initiator to trigger the “explosion” of nanobubbles and promote the 6S release. Furthermore,in vivoassessment results indicate that ultrasound-augmented 6S@NB-MUC16A can significantly improve the response of EOC to PTX and the inhibition ratio of tumor growth compared to the control-treated with PTX alone, and exhibit less toxicity to the critical organs. The ultrasound-augmented 6S@NB-MUC16A with less cytotoxicity could be a potentially useful nanosystem to surmount PTX resistance in EOC, which provides potential possibilities for the applications in the biological field.