Doxorubicin Delivery into Tumor Cells with Ultrasound and Microbubbles

Doxorubicin Delivery into Tumor Cells with Ultrasound and Microbubbles
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DOI:
10.1021/mp100397p
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发表时间:
2011-05-01
影响因子:
4.9
通讯作者:
Bouakaz, A.
Bouakaz, A.
中科院分区:
医学2区
文献类型:
--
作者:
Escoffre, J. M.;Piron, J.;Bouakaz, A.

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阿霉素是一种有效的化疗药物,但其严重的副作用限制了其应用。需要使用非侵入性技术的药物靶向递送以增加局部药物浓度并减少全身副作用。微泡辅助超声已经成为一种很有前途的无创局部给药策略。本研究的目的是评估阿霉素联合微泡辅助超声在人U-87 MG胶质母细胞瘤和MDA-MB-231乳腺癌细胞中的适用性和有效性。在本研究中,微泡辅助超声辅助阿霉素递送增强了乳腺癌和胶质母细胞瘤细胞的死亡,包括诱导细胞凋亡。评价了各种微泡,包括Vevo Micromarker、BR 14、SonoVue和实验聚合物壳微泡。结果表明,Vevo Micromarker微泡辅助超声可诱导阿霉素在胶质母细胞瘤和乳腺癌细胞死亡中的增强。聚乳酸壳PEG和Vevo Micromarker微泡分别是在U-87 MG和MDA-MB-231细胞中有效递送多柔比星的最佳微泡。此外,阿霉素和Vevo Micromarker微泡辅助超声诱导细胞凋亡进行了检查,结果显示声压高于600 kPa时有正增量。从体外研究中得出的结论显示了这种策略在体内应用的潜力。
Doxorubicin is a potent chemotherapeutic whose severe side effects limit its application. Drug-targeted delivery with noninvasive techniques is required to increase the drug concentration locally and to reduce systemic side effects. Microbubble-assisted ultrasound has become a promising strategy for noninvasive local drug delivery. The aim of this study is to evaluate the applicability and the effectiveness of administration of doxorubicin combined with microbubble-assisted ultrasound in human U-87MG glioblastoma and MDA-MB-231 breast cancer cells. In the present study, the doxorubicin delivery aided by microbubble-assisted ultrasound enhanced the death of breast cancer and glioblastoma cells, including the induction of apoptosis. Various microbubbles were evaluated including Vevo Micromarker, BR14, SonoVue and experimental polymer shelled microbubbles. The results showed that Vevo Micromarker microbubble-assisted ultrasound could induce an enhancement of doxorubicin in glioblastoma and breast cancer cell death. Polylactide-Shelled PEG and Vevo Micromarker microbubbles were the best microbubbles for efficient doxorubicin delivery in the U-87 MG and MDA-MB-231 cells, respectively. Moreover, the induction of apoptosis by doxorubicin and Vevo Micromarker microbubble-assisted ultrasound was examined and results showed a positive increment for acoustic pressures above 600 kPa. The conclusions drawn from in vitro study show the potential of this strategy for an in vivo application.