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Ultrasound-triggered imaging and drug delivery using microbubble-self-aggregate complexes
Journal of Biomaterials Science, Polymer Edition ( IF 3.6 ) Pub Date : 2021-09-22 , DOI: 10.1080/09205063.2021.1976362
In Jae Chung 1 , Hyungwon Moon 2 , Seong Ik Jeon 1 , Hak Jong Lee 2, 3 , Cheol-Hee Ahn 1
Affiliation  

Abstract

Co-delivery of microbubbles (MBs) with anticancer drugs is a promising theranostic approach that can enhance both the ultrasound contrast and local extravasation of drugs with the sonoporation effect. The simultaneous administration of MBs and hydrophobic drugs, however, is still challenging due to the limitations in drug loading or undesirable stabilization of MBs. In this research, MB-self-aggregate complexes (MB-SAs) were newly fabricated for the encapsulation of hydrophobic drugs, and their theranostic properties are investigated in vitro and in vivo. Glycol chitosan self-aggregates (GC-SAs) loaded with hydrophobic drugs or dyes were chemically conjugated on the surface MBs. Their conjugation ratio was determined to be 73.9%, and GC-SAs on MBs did not affect the stability of MBs. GC-SA attached MBs (GC@MBs) were successfully visualized with low-intensity insonation and showed enhanced cellular uptake via the sonoporation effect. In vivo biodistribution of GC@MBs was examined with tumor-bearing mice, confirming that their accumulation at the tumor site increased by 1.85 times after ultrasound irradiation. The anticancer drug-loaded GC@MBs also exhibited 10% higher cytotoxicity under ultrasound flash. In conclusion, it was expected that GC@MBs could be used both as an ultrasound contrast agent and a drug carrier even with conventional ultrasonic devices.



中文翻译:

使用微泡自聚集复合物的超声触发成像和药物输送

摘要

微泡 (MBs) 与抗癌药物的共同递送是一种很有前途的治疗诊断方法,它可以增强超声对比度和具有声孔效应的药物的局部外渗。然而,由于药物负载的限制或 MB 的不良稳定性,MB 和疏水性药物的同时给药仍然具有挑战性。在这项研究中,MB-自聚集复合物(MB-SAs)被新制造用于包封疏水性药物,并在体外体内研究了它们的治疗诊断特性。. 载有疏水性药物或染料的乙二醇壳聚糖自聚集体 (GC-SAs) 以化学方式结合在表面 MBs 上。确定它们的共轭率为 73.9%,MBs 上的 GC-SAs 不影响 MBs 的稳定性。GC-SA 附着的 MBs (GC@MBs) 成功地通过低强度声波可视化,并通过声孔效应显示出增强的细胞摄取。体内用荷瘤小鼠检查了 GC@MBs 的生物分布,证实它们在肿瘤部位的积累在超声照射后增加了 1.85 倍。负载抗癌药物的 GC@MBs 在超声闪光下也表现出高出 10% 的细胞毒性。总之,预计 GC@MBs 可以用作超声造影剂和药物载体,即使与传统的超声设备一起使用。

更新日期:2021-09-22
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