化学
弹性蛋白酶
体内
体外
劈理(地质)
丝氨酸蛋白酶
中性粒细胞弹性蛋白酶
癌症研究
蛋白酵素
跨膜蛋白
免疫系统
细胞生物学
药理学
生物化学
蛋白酶
酶
炎症
免疫学
生物
受体
断裂(地质)
古生物学
生物技术
作者
Chuanda Zhu,Hao Chen,Jingjing Gong,Song Xue,Lidong Gong,Zeliang Yang,Zhenyu Zhu,Qiang Zhang,Tiancheng Li,Ling Liang,Zhiqiang Lin
标识
DOI:10.1016/j.cej.2024.149902
摘要
Neutrophil elastase (ELANE) plays a vital role in recognizing and destroying various cancer cells by cleaving target proteins, making it a promising therapeutic option. However, in vivo therapeutic effectiveness of ELANE is limited due to its inadequate protein cleavage efficiency, lack of tumor tissue targeting, and susceptibility to serine protease inhibition. Drawing inspiration from the ways metal ions regulate protein functions and activities, a metal cofactor-based approach was employed to enhance target protein cleavage and antitumor effects, using porcine pancreatic elastase (PPE, an ELANE homolog) as a model drug in this study. In a nutshell, an elastase nanocomplex with enhanced cleavage activity (CAEN) was developed and optimized in vitro. Administered through inhalation, CAEN prevented the degradation of PPE in the biological environment and efficiently delivered it to tumor cells. By effectively cleaving the transmembrane protein CD95 with higher specificity compared to free PPE, CAEN induced significant apoptosis in lung cancer cells. Furthermore, the released metal ions could activate type I interferon in macrophages, further enhancing the local immune response within lung tumor tissues. Overall, this study presents a novel approach to substantially enhance the specificity of protein drugs in terms of drug delivery and pharmacological effects.
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