Reactive Oxygen Species-Responsive Liposomes via Boronate-Caged Phosphatidylethanolamine
Reactive Oxygen Species-Responsive Liposomes via Boronate-Caged Phosphatidylethanolamine
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DOI：
10.1021/acs.bioconjchem.0c00397
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发表时间：
2020-09-01
影响因子：
4.7
通讯作者：
Best, Michael D.
中科院分区：
文献类型：
--
作者：
Lou, Jinchao;Best, Michael D.
脂质体已被证明是有效的纳米载体，因为它们能够封装和递送各种各样的治疗货物。脂质体研究的一个关键目标是加强对患病部位内容物释放的控制。尽管已经探索了许多刺激物用于触发脂质体释放，但活性氧（ROS）由于其在生物学中的关键作用和在患病细胞中的过量而提供了极好的靶标，其受到的关注明显较少。在这里，我们报告了ROS响应脂质体平台，通过包含具有硼酸酯头基的脂质1和醌甲基化物（QM）生成自分解连接器连接到二油酰磷脂酰乙醇胺（DOPE）脂质支架上。基于双折射的染料释放测定验证了该系统能够在加入过氧化氢（H2O2）后释放疏水和亲水内容物。仔细研究了释放过程的细节，数据显示硼酸酯头基的氧化去除足以导致疏水性内容物释放，而亲水性货物泄漏需要DOPE的产生。这些结果表明，脂质1可以作为一个有前途的ROS响应性脂质体递送平台的控制释放。
Liposomes have proven to be effective nanocarriers due to their ability to encapsulate and deliver a wide variety of therapeutic cargo. A key goal of liposome research is to enhance control over content release at diseased sites. Though a number of stimuli have been explored for triggering liposomal release, reactive oxygen species (ROS), which have received significantly less attention, provide excellent targets due to their key roles in biology and overabundance in diseased cells. Here, we report a ROS-responsive liposome platform through the inclusion of lipid 1 bearing a boronate ester headgroup and a quinone-methide (QM) generating self-immolative linker attached onto a dioleoylphosphatidylethanolamine (DOPE) lipid scaffold. Fluorescence-based dye release assays validated that this system enables release of both hydrophobic and hydrophilic contents upon hydrogen peroxide (H2O2) addition. Details of the release process were carefully studied, and data showed that oxidative removal of the boronate headgroup is sufficient to result in hydrophobic content release, while production of DOPE is needed for hydrophilic cargo leakage. These results showcase that lipid 1 can serve as a promising ROS-responsive liposomal delivery platform for controlled release.