Lipid/PLGA Hybrid Microbubbles as a Versatile Platform for Noninvasive Image-Guided Targeted Drug Delivery
Lipid/PLGA Hybrid Microbubbles as a Versatile Platform for Noninvasive Image-Guided Targeted Drug Delivery
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脂质/PLGA 混合微泡作为无创图像引导靶向药物输送的多功能平台
DOI：
10.1021/acsami.9b10188
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发表时间：
2019-11-13
影响因子：
9.5
通讯作者：
Yan, Fei
中科院分区：
文献类型：
--
作者：
Chen, Yan;Liang, Yangbiao;Yan, Fei
近年来，微泡(MBS)已成为超声造影剂和药物传递的重要载体。然而，传统的脂基微球的药物包封率较低，而聚合物微球在对比剂成像和超声诱导药物释放方面的能力较弱。在这里，我们开发了一种新型的多孔脂/PLGA杂化MBS(Lid/PLGA MBS)，解决了MBS作为显像剂和药物载体的两难问题。通过调节泡沫壳的弹性，将脂类引入PLGA壳中，以碳酸氢铵为造气剂，设计了脂质/PLGA MBS。软化的壳层和多孔的气泡结构使其能够产生更强的谐波信号，更容易受到超声辐射，从而在体内外超声造影术和超声引发的MB破坏方面具有优异的性能。以阿霉素(Dox)为模型药物，制备了Dox载脂/PLGA MBS(Dox-lide/PLGA MBS)，并获得了较高的药物包封率。在荷瘤小鼠体内成功地实现了超声实时跟踪给药和指令控制药物释放。联合应用Dox-Lid/PLGA MBS联合超声照射后，肿瘤生长抑制作用明显增强，与单独使用Dox或单独使用Dox-Lid/PLGA MBS相比，差异有统计学意义。我们的研究为超声造影成像和药物输送应用提供了一个创新的多功能MBS平台。
Microbubbles (MBs) have recently emerged as promising theranostic carriers for ultrasound contrast imaging and drug delivery. However, conventional lipid-based MBs have a poor drug encapsulation efficiency, and polymer-based MBs show a weak capability in contrast imaging and ultrasound triggered drug release. Here, we developed a novel type of multiporous lipid/PLGA hybrid MBs (lipid/PLGA MBs) that solved the dilemma of MBs as imaging agents and drug carriers. The lipid/PLGA MBs were designed through regulating the elasticity of the bubble shells using lipids to incorporate into the PLGA shells and ammonium bicarbonate as a gas-generating agent. The softened shells and the porous bubble structure make them be able to generate stronger harmonic signals and be more vulnerable to ultrasound irradiation, leading to their excellent performance in ultrasound contrast imaging and ultrasound-triggered MB destruction in vitro and in vivo. By using doxorubicin (Dox) as a model drug, the Dox-loaded lipid/PLGA MBs (Dox-lipid/PLGA MBs) were prepared and achieved a high drug encapsulation efficiency. The real-time tracking of drug delivery and on-command controlled drug release by ultrasound were successfully realized in the tumor-bearing mice. A significantly enhanced tumor growth inhibition effect could be observed when using Dox-lipid/PLGA MBs combined with ultrasound irradiation, compared with free Dox and Dox-lipid/PLGA MBs without ultrasound. Our study provides an innovative multifunctional platform of MBs for ultrasound contrast imaging and drug delivery applications.