文献：

Puerarin-Loaded Liposomes Co-Modified by Ischemic Myocardium-Targeting Peptide and Triphenylphosphonium Cations Ameliorate Myocardial Ischemia-Reperfusion Injury

文献链接：

https://www.tandfonline.com/doi/full/10.2147/IJN.S468394#d1e256

作者：

Yan Wang , Fengmei Li , Shanshan Wei , Wenqun Li , Junyong Wu , Shengnan Li , Xiongbin Hu, Tiantian Tang, Xinyi Liu

相关产品：

DSPE-PEG-NHS（磷脂-聚乙二醇-活性酯）

DSPE-PEG-NH2（磷脂-聚乙二醇-氨基）
原文摘要：
Purpose: Mitochondrial damage may lead to uncontrolled oxidative stress and massive apoptosis, and thus plays a pivotal role in the pathological processes of myocardial ischemia-reperfusion (I/R) injury. However, it is difficult for the drugs such as puerarin (PUE) to reach the mitochondrial lesion due to lack of targeting ability, which seriously affects the expected efficacy of drug therapy for myocardial I/R injury.
Methods: We prepared triphenylphosphonium (TPP) cations and ischemic myocardium-targeting peptide (IMTP) co-modified puerarin-loaded liposomes (PUE@T/I-L), which effectively deliver the drug to mitochondria and improve the effectiveness of PUE in reducing myocardial I/R injury.
Results: In vitro test results showed that PUE@T/I-L had sustained release and excellent hemocompatibility. Fluorescence test results showed that TPP cations and IMTP double-modified liposomes (T/I-L) enhanced the intracellular uptake, escaped lysosomal capture and promoted drug targeting into the mitochondria. Notably, PUE@T/I-L inhibited the opening of the mitochondrial permeability transition pore, reduced intracellular reactive oxygen species (ROS) levels and increased superoxide dismutase (SOD) levels, thereby decreasing the percentage of Hoechst-positive cells and improving the survival of hypoxia-reoxygenated (H/R)-injured H9c2 cells. In a mouse myocardial I/R injury model, PUE@T/I-L showed a significant myocardial protective effect against myocardial I/R injury by protecting mitochondrial integrity, reducing myocardial apoptosis and decreasing infarct size.
Conclusion: This drug delivery system exhibited excellent mitochondrial targeting and reduction of myocardial apoptosis, which endowed it with good potential extension value in the precise treatment of myocardial I/R injury.   

DSPE - PEG - NHS 是一种化学试剂，名称是 1,2 -二硬脂酰- sn -甘油- 3 -磷酸乙醇胺- N - 羟基琥珀酰亚胺聚乙二醇酯（1,2 - Distearoyl - sn - Glycero - 3 - Phosphoethanolamine - N - Hydroxysuccinimide Polyethylene Glycol）。主要由三部分组成：DSPE（1,2 -二硬脂酰- sn -甘油- 3 -磷酸乙醇胺）部分是一种磷脂成分，具有亲脂性，能够与细胞膜等脂质结构相互作用；PEG（聚乙二醇）部分是一种聚合物链，具有良好的水溶性和生物相容性，可以增加化合物在水溶液中的稳定性，并且减少非特异性蛋白吸附等；NHS（N - 羟基琥珀酰亚胺）部分是一种活性酯，它能够与含有氨基（-NH₂）的分子发生反应，形成稳定的酰胺键。
DSPE - PEG - NH₂是由 1,2 - 二硬脂酰 - sn - 甘油 - 3 - 磷酸乙醇胺（DSPE）、聚乙二醇（PEG）和氨基（-NH₂）组成。DSPE 部分是一种磷脂，具有两条长的疏水脂肪酸链（硬脂酸），可以插入脂质双层中或者与其他疏水性分子相互作用。PEG 部分是一种亲水性的聚合物链，能增加整个分子在水溶液中的溶解性和稳定性，并且可以减少非特异性吸附。氨基则是一个活性官能团，可以参与多种化学反应。基于DSPE - PEG - NHS 、DSPE - PEG - NH₂的相关性能，脂质体PUE@T/IL的合成如下：

将大豆卵磷脂（SL）、胆固醇（Chol）、TPP-PEG-PE和IMTP-PEG-PE以一定的摩尔比混合。混合物和PUE完全溶解在色谱甲醇中，旋转蒸发后附着在小瓶底部，可以观察到在小瓶底部形成均匀的薄膜。加入适量的蒸馏水或PBS水合并超声处理使薄膜水化。最后，脂质悬浮液首先通过微孔滤膜过滤，然后通过较大的孔径聚碳酸酯膜挤出，以获得均匀粒径的PUE@T/I-L。同样地，采用上述相同方法制备了载有PUE的脂质体（PUE@L）、由TPP修饰的载有PUE的脂质体（PUE@T-L）和由IMTP修饰的载有PUE的脂质体（PUE@I-L）。同样，使用相似的方法，用香豆素-6（荧光探针，C6）代替PUE制备了C6标记的脂质体。

结论：
该文献成功制备出基于DSPE - PEG - NHS 、DSPE - PEG - NH₂合成的脂质体PUE@T/IL。结果表明PUE@T/IL具有缓释性和良好的相容性，并能抑制线粒体通透性转换孔的开放，降低细胞内活性氧（ROS）水平并增加超氧化物歧化酶（SOD）水平，从而降低Hoechst阳性细胞的百分比，提高缺氧生存率-再氧合(H/R)损伤的H9c2细胞。