Ultrasound-mediated destruction of LHRHa-targeted and paclitaxel-loaded lipid microbubbles induces proliferation inhibition and apoptosis in ovarian cancer cells.
Ultrasound-mediated destruction of LHRHa-targeted and paclitaxel-loaded lipid microbubbles induces proliferation inhibition and apoptosis in ovarian cancer cells.
复制标题
超声介导的 LHRHa 靶向和负载紫杉醇脂质微泡的破坏诱导卵巢癌细胞的增殖抑制和凋亡
DOI：
10.1021/mp4005244
复制
发表时间：
2014-01-06
影响因子：
4.9
通讯作者：
Xu RX
中科院分区：
文献类型：
--
作者：
Liu H;Chang S;Sun J;Zhu S;Pu C;Zhu Y;Wang Z;Xu RX
尽管紫杉醇(PTX)联合铂类药物作为治疗卵巢癌的一线化疗方案，但其临床疗效往往受到严重不良反应的限制。超声靶向微泡破坏(UTMD)技术在减少副作用、提高治疗效果方面具有广阔的应用前景。然而，该技术通常使用非靶向微泡，效率不佳。我们合成了靶向和PTX负载的微泡(MBS)，用于UTMD介导的卵巢癌细胞化疗。通过生物素-亲和素连接将促黄体激素释放激素类似物(LHRHa)包被PTX负载的脂质MBS，以靶向表达LHRH受体的卵巢癌A2780/DDP细胞。在细胞培养研究中，PTX和LHRHa靶向MBS(TPLMBs)联合超声(300 kHz，0.5W/cm2，30s)处理后24、48和72 h的抗增殖活性分别为41.30±3.93%、67.76±2.45%和75.93±2.81%。治疗后24小时细胞凋亡率为32.6±0.79%，明显高于单纯PTX组和非靶向PTX负载MBS(NPLMBs)组(P<0.05)。我们的实验验证了超声介导卵巢癌靶向和载药MBS将提高PTX治疗效率的假设。
Although paclitaxel (PTX) is used with platinum as the first line chemotherapy regimen for ovarian cancer, its clinical efficacy is often limited by severe adverse effects. Ultrasound targeted microbubble destruction (UTMD) technique holds a great promise in minimizing the side effects and maximizing the therapeutic efficacy. However, the technique typically uses non-targeted microbubbles with suboptimal efficiency. We synthesized targeted and PTX-loaded microbubbles (MBs) for UTMD mediated chemotherapy in ovarian cancer cells. PTX-loaded lipid MBs were coated with a luteinizing hormone-releasing hormone analogue (LHRHa) through a biotin-avidin linkage to target the ovarian cancer A2780/DDP cells that express the LHRH receptor. In the cell culture studies, PTX-loaded and LHRHa targeted MBs (TPLMBs) in combination with ultrasound (300 kHz, 0.5 W/cm2, 30 seconds) demonstrated anti-proliferative activities of 41.30 ± 3.93%, 67.76 ± 2.45%, and 75.93 ± 2.81% at 24 hours, 48 hours, and 72 hours after the treatment, respectively. The cell apoptosis ratio at 24 hours after the treatment is 32.6 ± 0.79 %, which is significantly higher than other treatment groups such as PTX only and no-targeted PTX-loaded MBs (NPLMBs) with or without ultrasound mediation. Our experiment verifies the hypothesis that ultrasound mediation of ovarian cancer targeted and drug loaded MBs will enhance the PTX therapeutic efficiency.
登录
查看更多内容
影响因子：
6.7
作者：
Anderson CR;Rychak JJ;Backer M;Backer J;Ley K;Klibanov AL
通讯作者：
Klibanov AL
影响因子：
4.9
作者：
Geers, Bart;Lentacker, I.;De Smedt, Stefaan C.
通讯作者：
De Smedt, Stefaan C.
影响因子：
5.7
作者：
Gomez, Lourdes A.;de las Pozas, Alicia;Perez-Stable, Carlos
通讯作者：
Perez-Stable, Carlos
影响因子：
4.9
作者：
Escoffre, J. M.;Piron, J.;Bouakaz, A.
通讯作者：
Bouakaz, A.
影响因子：
10.8
作者：
Dharap, SS;Qiu, B;Minko, T
通讯作者：
Minko, T