Surface modification of PGP for a neutrophil-nanoparticle co-vehicle to enhance the anti-depressant effect of baicalein.
Surface modification of PGP for a neutrophil-nanoparticle co-vehicle to enhance the anti-depressant effect of baicalein.
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DOI：
10.1016/j.apsb.2017.11.012
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发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Qin J
中科院分区：
文献类型：
--
作者：
Chen B;Luo M;Liang J;Zhang C;Gao C;Wang J;Wang J;Li Y;Xu D;Liu L;Zhang N;Chen H;Qin J
利用细胞作为载体与纳米颗粒相结合的疗法近年来引起了世界越来越多的关注。红细胞、白细胞和干细胞已被用于肿瘤免疫治疗、组织再生和炎症性疾病，并且众所周知，中性粒细胞可以在包括抑郁症在内的许多脑部疾病的脑部病变中积聚。 N-乙酰 Pro-Gly-Pro (PGP) 肽通过 CXCR2 受体与中性粒细胞表现出高特异性结合亲和力。在这项研究中，PGP被用来修饰黄芩素负载的固体脂质纳米颗粒（PGP-SLN），以促进与体内中性粒细胞的结合。通过增加 BLA 中黄芩素的浓度，证明了脑靶向递送至基底外侧杏仁核 (BLA)。在体外和体内观察到增强的抗抑郁作用。其机制涉及抑制细胞凋亡和减少乳酸脱氢酶的释放。对大鼠进行的行为评估表明，达到了抗抑郁效果。结果表明，PGP-SLN 减少了嗅球切除 (OB) 大鼠的不动时间，增加了游泳时间和攀爬时间，并减弱了运动能力。总之，PGP 修饰是一种利用细胞纳米颗粒递送系统靶向大脑来治疗抑郁症的策略。 PGP 用于修饰负载黄芩素的固体脂质纳米颗粒（PGP-SLN），以便在体内与中性粒细胞结合。在体外和体内获得了细胞纳米颗粒大脑靶向递送至基底外侧杏仁核并增强的抗抑郁作用。其机制涉及抑制线粒体诱导的细胞凋亡和减少乳酸脱氢酶的释放。
Exploiting cells as vehicles combined with nanoparticles combined with therapy has attracted increasing attention in the world recently. Red blood cells, leukocytes and stem cells have been used for tumor immunotherapy, tissue regeneration and inflammatory disorders, and it is known that neutrophils can accumulate in brain lesions in many brain diseases including depression. N-Acetyl Pro–Gly–Pro (PGP) peptide shows high specific binding affinity to neutrophils through the CXCR2 receptor. In this study, PGP was used to modify baicalein-loaded solid lipid nanoparticles (PGP-SLNs) to facilitate binding to neutrophils in vivo. Brain-targeted delivery to the basolateral amygdala (BLA) was demonstrated by enhanced concentration of baicalein in the BLA. An enhanced anti-depressant effect was observed in vitro and in vivo. The mechanism involved inhibition of apoptosis and a decrease in lactate dehydrogenase release. Behavioral evaluation carried out with rats demonstrated that anti-depression outcomes were achieved. The results indicate that PGP-SLNs decrease immobility time, increase swimming time and climbing time and attenuate locomotion in olfactory-bulbectomized (OB) rats. In conclusion, PGP modification is a strategy for targeting the brain with a cell–nanoparticle delivery system for depression therapy. PGP was used to modify solid lipid nanoparticles (PGP-SLNs) loaded with baicalein for binding to neutrophils in vivo. Cell–nanoparticle brain-targeted delivery to the basolateral amygdala and increased anti-depressant effect was obtained in vitro and in vivo. The mechanism involved inhibition of apoptosis induced by mitochondria and reduction of lactate dehydrogenase release.
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