文献：Nano-encapsulated tanshinone IIA in PLGA-PEG-COOH inhibits apoptosis and inflammation in cerebral ischemia/reperfusion injury

作者：Xin Zhang , Xutong Zhu , Lifa Huang , Zupeng Chen , Yuchen Wang EMAIL logo , Yajun Liu , Ruihan Pan and Ling L

文献链接：https://www.degruyterbrill.com/document/doi/10.1515/gps-2022-8156/html

摘要：

Tanshinone IIA has a potential therapeutic effect on cerebral ischemia/reperfusion injury (CIRI). In this study, tanshinone IIA was encapsulated in poly(lactic-co-glycolic acid)-block-poly (ethylene glycol)-carboxylic acid (PLGA-PEG-COOH) nanoparticles, and its therapeutic efficacy on CIRI was investigated. Morphology and dynamic light scattering analyses were performed to identify and optimize nano-formulations. A drug release test was conducted using the dialysis method. The cytotoxic effect of tanshinone IIA on human neuroblastoma cells (SH-SY5Y) and brain endothelial capillary cells (hCMEC/D3) was measured using the MTT assay. The protective effect of PLGA-PEG-COOH-encapsulated tanshinone IIA against CIRI was evaluated in oxygen and glucose deprivation/reoxygenation-induced SH-SY5Y/IR cells and middle cerebral artery occlusion (MCAO) rats. Results showed that PLGA-PEG-COOH-encapsulated tanshinone IIA promoted viability and inhibited apoptosis of SH-SY5Y/IR cells (P < 0.01). Moreover, PLGA-PEG-COOH-encapsulated tanshinone IIA facilitated the invasion of SH-SY5Y/IR cells and repressed inflammation in MCAO rats (P < 0.01). Noteworthy, PLGA-PEG-COOH-encapsulated tanshinone IIA combined with angiopep-2 peptide presented a better inhibitory effect on CIRI than tanshinone IIA alone (P < 0.01). Angiopep-2 peptide contributes to traversing blood–brain barrier by recognizing lipoprotein-related protein expressed in the brain capillary endothelial cells. In conclusion, PLGA-PEG-COOH-encapsulated tanshinone IIA plus angiopep-2 peptide holds promising therapeutic potential toward CIRI.

本研究将丹参酮IIA包裹在聚乳酸-羟基乙酸嵌段聚乙二醇-羧酸（PLGA-PEG-COOH）纳米颗粒中，并研究其对CIRI的治疗效果。进行形态学和动态光散射分析以鉴定和优化纳米制剂。使用透析法进行药物释放试验。

采用MTT法测定丹参酮IIA对人神经母细胞瘤细胞（SH-SY5Y）和脑内皮毛细血管细胞（hCMEC/D3）的细胞毒性作用。在缺氧和葡萄糖剥夺/复氧诱导的SH-SY5Y/IR细胞和大脑中动脉闭塞（MCAO）大鼠中评估了PLGA-PEG-COOH包裹的丹参酮IIA对CIRI的保护作用。

结果表明，PLGA-PEG-COOH包裹丹参酮IIA可促进SH-SY5Y/IR细胞的存活并抑制其凋亡（P<0.01）。此外，PLGA-PEG-COOH包裹的丹参酮IIA促进了SH-SY5Y/IR细胞的侵袭，并抑制了MCAO大鼠（P<0.01）。

值得注意的是，PLGA-PEG-COOH包裹的丹参酮IIA与血管肽-2肽联合使用对CIRI的抑制作用优于单独使用丹参酮IIA（P<0.01）。Angiopep-2肽通过识别脑毛细血管内皮细胞中表达的脂蛋白相关蛋白，有助于穿越血脑屏障。

总之，PLGA-PEG-COOH包裹的丹参酮IIA和血管肽-2肽对CIRI具有很好的治疗潜力。

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