Development and evaluation of an ultrasound-triggered microbubble combined transarterial chemoembolization (TACE) formulation on rabbit VX2 liver cancer model

超声触发微泡联合经动脉化疗栓塞 (TACE) 制剂对兔 VX2 肝癌模型的开发和评估

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作者:Doyeon Kim, Jae Hwan Lee, Hyungwon Moon, Minkyu Seo, Hyounkoo Han, Hongkeun Yoo, Howon Seo, Jingu Lee, Sujung Hong, Pilhan Kim, Hak Jong Lee, Jin Wook Chung, Hyuncheol Kim

Conclusion

Incorporation of doxorubicin-loaded microbubble in the TACE formulation facilitated drug delivery to the tumor with real-time monitoring and enhanced the therapeutic efficacy of TACE. Thus, the enhanced TACE formulation may represent a new treatment strategy against liver cancer.

Methods

To overcome these limitations, a doxorubicin-loaded albumin nanoparticle-conjugated microbubble complex in an iodized oil emulsion (DOX-NPs-MB complex in Lipiodol) has been developed as a new ultrasound-triggered TACE formulation.

Results

(1) Microbubbles enhanced therapeutic efficacy by effectively delivering doxorubicin- loaded nanoparticles into liver tumors via sonoporation under ultrasound irradiation (US+). (2) Microbubbles constituting the complex retained their function as an ultrasound contrast agent in Lipiodol. In a rabbit VX2 liver cancer model, the in vivo study of DOX-NPs-MB complex in Lipiodol (US+) decreased the viability of tumor more than the conventional TACE formulation, and in particular, effectively killed cancer cells in the tumor periphery.

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