文獻：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

文獻鏈接：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.

本研究將丹參酮IIA包裹在聚乳酸-羥基乙酸嵌段聚乙二醇-羧酸（PLGA-PEG-COOH）納米顆粒中，并研究其對CIRI的治療效果。進行形態(tài)學(xué)和動態(tài)光散射分析以鑒定和優(yōu)化納米制劑。使用透析法進行藥物釋放試驗。

采用MTT法測定丹參酮IIA對人神經(jīng)母細胞瘤細胞（SH-SY5Y）和腦內(nèi)皮毛細血管細胞（hCMEC/D3）的細胞毒性作用。在缺氧和葡萄糖剝奪/復(fù)氧誘導(dǎo)的SH-SY5Y/IR細胞和大腦中動脈閉塞（MCAO）大鼠中評估了PLGA-PEG-COOH包裹的丹參酮IIA對CIRI的保護作用。

結(jié)果表明，PLGA-PEG-COOH包裹丹參酮IIA可促進SH-SY5Y/IR細胞的存活并抑制其凋亡（P<0.01）。此外，PLGA-PEG-COOH包裹的丹參酮IIA促進了SH-SY5Y/IR細胞的侵襲，并抑制了MCAO大鼠（P<0.01）。

值得注意的是，PLGA-PEG-COOH包裹的丹參酮IIA與血管肽-2肽聯(lián)合使用對CIRI的抑制作用優(yōu)于單獨使用丹參酮IIA（P<0.01）。Angiopep-2肽通過識別腦毛細血管內(nèi)皮細胞中表達的脂蛋白相關(guān)蛋白，有助于穿越血腦屏障。

總之，PLGA-PEG-COOH包裹的丹參酮IIA和血管肽-2肽對CIRI具有很好的治療潛力。

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