脂质氧化途径在活性氧介导的脂质体货物释放中的作用。

IF 5.2 Q2 MATERIALS SCIENCE, MULTIDISCIPLINARY
Olga Lem, Roosa Kekki, Artturi Koivuniemi, Alexander Efimov, Timo Laaksonen and Nikita Durandin
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引用次数: 0

摘要

活性氧(ROS)介导的光氧化反应是引发脂质体释放药物的有效方法。除了释放小分子外,它还能释放大分子,使其成为控制药物释放的多功能工具。然而,ROS 敏感脂质体释放大分子的确切机制仍不清楚。目前还没有关于脂质氧化对不同大小的货物分子释放影响的研究。通过 HPLC-HRMS 方法,我们分析了酞菁负载的 DOTAP:Cholesterol:DSPE-PEG 脂质体中对 ROS 敏感的 DOTAP 脂质在不同持续时间的 630 纳米光照射后的氧化产物。较短的照射时间(1-2 分钟)主要形成氢过氧化物和沧醇。照射时间较长(9 分钟)则会产生醛。有趣的是,脂质双分子层中环氧化物/一氢过氧化物和沧醇的存在确保了 90% 的亲水性小分子(如钙黄绿素)的释放,而不是大分子(≥10 KDa)的释放。氧化至醛类是释放 10-70 kDa 右旋糖酐的必要条件,释放效率约为 30%。分子动力学模拟显示,醛的形成是形成孔隙甚至完全破坏脂膜的必要条件,而氢过氧化物的存在则足以使双层膜对水和小分子具有更高的渗透性。这一重要发现揭示了 ROS 敏感给药系统释放不同药物分子的机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

The role of lipid oxidation pathway in reactive oxygen species-mediated cargo release from liposomes†

The role of lipid oxidation pathway in reactive oxygen species-mediated cargo release from liposomes†

Reactive oxygen species (ROS)-mediated photooxidation is an efficient method for triggering a drug release from liposomes. In addition to the release of small molecules, it also allows the release of large macromolecules, making it a versatile tool for controlled drug delivery. However, the exact release mechanism of large macromolecules from ROS-sensitive liposomes is still unclear. There are no studies on the effect of lipid oxidation on the release of cargo molecules of different sizes. By using HPLC-HRMS method we analyzed the oxidation products of ROS-sensitive DOTAP lipid in phthalocyanine-loaded DOTAP:Cholesterol:DSPE-PEG liposomes after 630 nm light irradiation of different durations. Shorter illumination time (1–2 minutes) led to the formation of hydroperoxides and vic-alcohols predominantly. Longer 9-minute irradiation resulted already in aldehydes generation. Interestingly, the presence of epoxides/mono-hydroperoxides and vic-alcohols in a lipid bilayer ensured a high 90% release of small hydrophilic cargo molecules i.e. calcein, but not large (≥10 KDa) macromolecules. Oxidation till aldehydes was mandatory to deliver e.g. dextrans of 10–70 kDa with ca. 30% efficiency. Molecular dynamics simulations revealed that the formation of aldehydes is required to form pores or even fully disrupt the lipid membrane, while e.g. presence of hydroperoxides is enough to make the bilayer more permeable just for water and small molecules. This is an important finding that shed a light on the release mechanism of different cargo molecules from ROS-sensitive drug delivery systems.

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来源期刊
Materials Advances
Materials Advances MATERIALS SCIENCE, MULTIDISCIPLINARY-
CiteScore
7.60
自引率
2.00%
发文量
665
审稿时长
5 weeks
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