Platelet-inspired nanomedicine targeting activated neutrophils to alleviate ulcerative colitis by free radicals scavenging and controlled neutrophil swarming
Platelet-inspired nanomedicine targeting activated neutrophils to alleviate ulcerative colitis by free radicals scavenging and controlled neutrophil swarming
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DOI：
10.1016/j.nantod.2023.102139
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发表时间：
2024-02
期刊：
影响因子：
17.4
通讯作者：
Xiangji Yan;Jian Song;Yujie Zhang;Mei Yang;Zhichao Deng;Bowen Gao;Yuanyuan Zhu;Chenxi Xu;Chenguang Ding;Mingzhen Zhang;Baojun Zhang
中科院分区：
文献类型：
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作者：
Xiangji Yan;Jian Song;Yujie Zhang;Mei Yang;Zhichao Deng;Bowen Gao;Yuanyuan Zhu;Chenxi Xu;Chenguang Ding;Mingzhen Zhang;Baojun Zhang
溃疡性结肠炎(UC)是一种慢性非特异性炎症性疾病，导致肠道炎症和溃疡。目前的治疗方法侧重于在短期内缓解症状，而在临床上迫切需要实现炎症的长期缓解。在本研究中，我们成功地合成了具有级联超氧化物歧化酶/过氧化氢酶活性的铂掺杂碳纳米点纳米酶(PtCD)。将PtCD和脾酪氨酸激酶(SYK)抑制剂PtCD共负载到PLGA中，并与血小板膜包裹，形成了一种血小板诱导的纳米药物(PM@Pic/PtCD@NP)。PtCD纳米粒(PtCD@NP)可与线粒体共定位，清除活性氧(ROS)，减少促炎细胞因子的表达。此外，血小板膜的仿生修饰使PM@Pic/PtCD@NP能够搭便车将中性粒细胞送到炎症部位，并释放皮卡特诺来抑制中性粒细胞的聚集。静脉注射PM@Pic/PtCD@NP可部分逆转和预防结肠炎小鼠模型的肠道炎症和肠屏障功能障碍。序列分析表明，线粒体呼吸链复合体Ⅰ的基因标记与PM@Pic/PtCD@NP处理显著相关。总而言之，这项研究表明PM@Pic/PtCD@NP治疗可能作为UC长期缓解的一种创新治疗策略。
Ulcerative colitis (UC) is a chronic non-specific inflammatory disease that causes inflammation and ulcers in the intestinal tract. Current therapies focus on the relief of symptoms in the short-term while it is an urgent need to achieve long-term remission of inflammation in clinics. In the current study,Platinum-dopedcarbon nanodot (CD) nanozymes (PtCD) with cascade enzymatic activities for superoxide dismutase/catalase (SOD/CAT) were successfully synthesized. PtCD and spleen tyrosine kinase (SYK) inhibitor piceatannol were co-loaded in PLGA and coated with platelet membrane to form a platelet-inspired nanomedicine (PM@Pic/PtCD@NP). PtCD-loaded nanoparticles (PtCD@NP) were found to co-locate with mitochondria, scavenge reactive oxygen species (ROS), and reduce the expression of pro-inflammatory cytokines. In addition, the biomimetic modification with the platelet membrane enabled PM@Pic/PtCD@NP to hitchhike neutrophils to the site of inflammation and release piceatannol to inhibit neutrophil swarming. Intravenous administration of PM@Pic/PtCD@NP partially reversed and prevented intestinal inflammation and intestinal barrier dysfunction in a murine model of colitis. The RNA-sequencing analysis revealed that gene markers of mitochondrial respiratory chain complex Ⅰ were significantly associated with PM@Pic/PtCD@NP treatment. Collectively, This study suggests that PM@Pic/PtCD@NP treatment may serve as an innovative therapeutic strategy for the long-term remission of UC.