文献：Self-assembled liposome-loaded microbubbles: The missing link for safe and efficient ultrasound triggered drug-delivery

文献链接：https://www.sciencedirect.com/science/article/abs/pii/S016836591100109X

作者：Bart Geers a, Ine Lentacker a, Niek N. Sanders b, Joseph Demeester a, Stephen Meairs c, Stefaan C. De Smedt a

摘要：

Liposome-loaded microbubbles have been recently introduced as a promising drug delivery platform for ultrasound guided drug delivery. In this paper we design liposome-loaded (lipid-shelled) microbubbles through the simple self-assembly of the involved compounds in a single step process. We thoroughly characterized the liposome-loading of the microbubbles and evaluated the cell killing efficiency of this material using doxorubicin (DOX) as a model drug. Importantly, we observed that the DOX liposome-loaded microbubbles allowed killing of melanoma cells even at very low doses of DOX. These findings clearly prove the potential of liposome-loaded microbubbles for ultrasound targeted drug delivery to cancer tissues.

功能化微泡的制备与表征

“功能化微泡”（即含有巯基功能化PEG脂质的微泡）是从1,2-二棕榈酰基-sn-甘油-3-磷酸胆碱（DPPC）和1,2-二硬脂酰基-sn-丙三醇胺-N-[PDP（聚乙二醇）-2000]（DSPE-PEG-SPDP）（Avanti极性脂质，阿尔拜斯特，AL）在1:2:7甘油-丙二醇-H2O溶剂（Sigma aldrich，Bornem，Belgium）中的脂质溶液开始制备的，脂质溶液中脂质的摩尔比分别为

脂质体自组装微泡的制备

如图1所示，为了制备负载脂质体的微泡，向（官能化）脂质DPPC和DSPE-PEG-SPDP的混合物中加入含有DSPE-PEG-MALEIMIDE的脂质体，将其溶解在甘油-丙二醇-水溶剂中，浓度低于其临界胶束浓度。

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DSPE-PEG-cRGD

DPPE-PEG-cRGD

DMPE-PEG-cRGD

DOPE-PEG-cRGD

DPPE-PEG-RGD

DMPE-PEG-RGD

DOPE-PEG-RGD

4-Arm PEG-DSPE

C12-PEG-COOH

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