Mechanisms of enhanced drug delivery in brain metastases with focused ultrasound-induced blood-tumor barrier disruption
Mechanisms of enhanced drug delivery in brain metastases with focused ultrasound-induced blood-tumor barrier disruption
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DOI：
10.1073/pnas.1807105115
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发表时间：
2018-09-11
影响因子：
11.1
通讯作者：
Jain, Rakesh K.
中科院分区：
文献类型：
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作者：
Arvanitis, Costas D.;Askoxylakis, Vasileios;Jain, Rakesh K.
血-脑/血-肿瘤屏障(BBB和BTB)和间质运输可能是脑肿瘤治疗药物运输的主要障碍。在这项研究中，我们研究了聚焦超声(FUS)结合微泡对两种相关的化疗药物在细胞分辨率下在乳腺癌脑转移瘤中的传输的影响：非靶向化疗药物阿霉素和抗体-药物结合物阿曲珠单抗(T-DM1)。使用HER2阳性乳腺癌脑转移的原位异种移植模型和定量显微镜，我们显示两种药物的外渗量显著增加(阿霉素和T-DM1分别增加7倍和2倍)，我们提供了药物渗透性增加的证据(>；100 vs.
Blood-brain/blood-tumor barriers (BBB and BTB) and interstitial transport may constitute major obstacles to the transport of therapeutics in brain tumors. In this study, we examined the impact of focused ultrasound (FUS) in combination with microbubbles on the transport of two relevant chemotherapy-based anticancer agents in breast cancer brain metastases at cellular resolution: doxorubicin, a nontargeted chemotherapeutic, and ado-trastuzumab emtansine (T-DM1), an antibody-drug conjugate. Using an orthotopic xenograft model of HER2-positive breast cancer brain metastasis and quantitative microscopy, we demonstrate significant increases in the extravasation of both agents (sevenfold and twofold for doxorubicin and T-DM1, respectively), and we provide evidence of increased drug penetration (>100 vs.