Trastuzumab-Targeted Biodegradable Nanoparticles for Enhanced Delivery of Dasatinib in HER2+Metastasic Breast Cancer
Trastuzumab-Targeted Biodegradable Nanoparticles for Enhanced Delivery of Dasatinib in HER2+Metastasic Breast Cancer
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DOI：
10.3390/nano9121793
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发表时间：
2019-12-01
期刊：
影响因子：
5.3
通讯作者：
Alonso-Moreno, Carlos
中科院分区：
文献类型：
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作者：
Niza, Enrique;del Mar Noblejas-Lopez, Maria;Alonso-Moreno, Carlos
达沙替尼 (DAS) 是一种多激酶抑制剂，作用于多种信号激酶。 DAS 用作慢性加速性粒细胞白血病和费城染色体阳性急性淋巴细胞白血病的二线治疗。 DAS 在其他实体瘤中的治疗潜力正在评估中。对于许多其他化合物来说，其药代动力学和递送特性的改进可能会增强疗效。抗体靶向的可生物降解纳米颗粒可用于靶向癌症治疗。 DAS 在人表皮生长因子受体 2 (HER2) 阳性肿瘤中显示出活性，因此使用纳米载体将该化合物与抗 HER2 抗体曲妥珠单抗 (TAB) 结合可以提高其疗效。 TAB 靶向的负载 DAS 的纳米粒子是通过纳米技术生成的。引导纳米载体增强了 DAS 对 HER2 人乳腺癌细胞系的体外细胞毒性。进行了细胞机制、释放研究和纳米颗粒稳定性，为将负载 DAS 的 TAB 靶向纳米颗粒定位为进一步开发 HER2 过表达乳腺癌治疗的潜在策略提供证据。
Dasatinib (DAS) is a multikinase inhibitor that acts on several signaling kinases. DAS is used as a second-line treatment for chronic accelerated myeloid and Philadelphia chromosome-positive acute lymphoblastic leukemia. The therapeutic potential of DAS in other solid tumours is under evaluation. As for many other compounds, an improvement in their pharmacokinetic and delivery properties would potential augment the efficacy. Antibody-targeted biodegradable nanoparticles can be useful in targeted cancer therapy. DAS has shown activity in human epidermal growth factor receptor 2 (HER2) positive tumors, so conjugation of this compound with the anti-HER2 antibody trastuzumab (TAB) with the use of nanocarriers could improve its efficacy. TAB-targeted DAS-loaded nanoparticles were generated by nanotechnology. The guided nanocarriers enhanced in vitro cytotoxicity of DAS against HER2 human breast cancer cell lines. Cellular mechanistic, release studies and nanoparticles stability were undertaken to provide evidences for positioning DAS-loaded TAB-targeted nanoparticles as a potential strategy for further development in HER2-overexpressing breast cancer therapy.