Hongxing Shi, Yaoyu Guo, Chong Geng, Lin Chen, Shuai He, Wenxuan He, Yanbai Chen, Yau Kei Chan, Chunhui Wang, Yi Deng
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引用次数: 0
摘要
急性胰腺炎(AP)是全球最严重的致命性炎症之一,其特点是活性氧(ROS)诱导的炎症和胰酶(PEs)过度激活。由于 ROS 诱导的 PE 会加剧 AP 的恶化,因此清除 PE 内的 ROS 是治疗 AP 的先决条件。为了解决这个棘手的问题,我们设计了由 Mo2C-Au (MA)、磷脂和蛋白酶抑制剂组成的工程生物异质结(bio-HJs)。首先,经过装饰的磷脂和蛋白酶抑制剂有助于向炎症胰腺输送 MA 并中和 PE。其次,MA 表现出卓越的抗氧化和清除 ROS 能力,这主要得益于 Mo2C 与金之间的电子转移增加了 Mo 上的空轨道,理论计算证实了这一点。体外实验证明,生物 HJ 具有出色的生物相容性、优异的胰蛋白酶中和能力和高效的 ROS 清除能力。更令人鼓舞的是,体内研究进一步表明,生物 HJ 可通过抑制 ROS 诱导的 TLR4-ERK1/2 MAPK-MLCK 炎症信号通路的激活,阻止炎症细胞的浸润,减轻 AP 的严重程度。正如所设想的那样,工程生物 HJ 是治疗和预防 AP 的一种很有前景的方法。
Engineered Bio‐Heterojunction with Robust ROS‐Scavenging and Anti‐Inflammation for Targeted Acute Pancreatitis Therapy
Acute pancreatitis (AP) is one of the most severe mortal inflammatory diseases worldwide, which is characterized by the over‐activation of reactive oxygen species (ROS)‐induced inflammation and pancreatic enzymes (PEs). As the PEs induced by ROS exacerbate the progression of AP, therefore, scavenging ROS within PEs is a prerequisite for AP treatment. To address the daunting issue, the engineered bio‐heterojunctions (bio‐HJs) consisting of Mo2C‐Au (MA), phospholipid, and protease inhibitors are devised. First, the decorated phospholipid and protease inhibitors facilitate the delivery of MA to the inflammatory pancreas as well as neutralization of PEs. Next, the MA exhibits outstanding antioxidant and ROS scavenging abilities, primarily benefiting from the increased empty orbitals on Mo attributed to electron transfer between the Mo2C and Au confirmed by theoretical calculation. The in vitro experiments demonstrate that the bio‐HJs exhibit splendid biocompatibility, excellent trypsin neutralization, and efficient ROS elimination properties. More encouragingly, the in vivo studies further reveal that the bio‐HJs prevent the infiltration of inflammatory cells and alleviate the severity of AP by suppressing the ROS‐induced activation of the TLR4‐ERK1/2 MAPK‐MLCK inflammatory signaling pathway. As envisioned, the engineered bio‐HJs represent a promising approach to the treatment and prevention of AP.
期刊介绍:
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