Enhanced antitumor efficacy of fresh pig spleen extracts (PAT) encapsulated with cytidinyl and cationic lipid nanocomplexes  

中性胞苷/阳离子脂质递送猪脾提取物(PAT)发挥强效抗肿瘤作用

作　　者：Xiaotong Yu Jing Wu Qi Zhang Jiamei Hong Jing Yu Zhu Guan Yanhui Yin Zhenjun Yang 于小桐;吴静;张琦;洪佳美;于晶;关注;尹艳慧;杨振军(北京大学药学院天然药物及仿生药物全国重点实验室,北京100191;北京大学基础医学院免疫学系卫生部医学免疫学重点实验室,北京100191)

机构地区：[1]State Key Laboratory of Natural&Biomimetic Drugs,School of Pharmaceutical Sciences,Peking University,Beijing 100191,China [2]Department of Immunology,School of Basic Medical Sciences,Key Laboratory of Medical Immunology of Ministry of Health,PekingUniversity,Beijing 100191,China

出　　处：《Journal of Chinese Pharmaceutical Sciences》2025年第1期14-27,共14页中国药学(英文版)

基　　金：The Contract Grant from Zhejiang Fengan Biopharmaceutical Co.,Ltd,Zhejiang Province,China。

摘　　要：Traditional Chinese Medicine(TCM)has been utilized in China for thousands of years to treat and prevent various diseases,with recent research highlighting microRNAs(miRNAs)in herbal decoctions as key bioactive components.The oral lyophilized powder of the pig spleen extracts(PAT)composed of oligonucleotides and peptides extracted from fresh pig spleen and delivered via a lipid mixture containing neutral cytidinyl lipid DNCA and cationic lipid CLD(Mix),has demonstrated significant antitumor effects against A549 and BCPAP cells,promoting early and late apoptosis by approximately 20%in A549 cells.Intratumoral administration of PAT/Mix in A549-bearing mice significantly reduced both tumor volume and weight.Transcriptomic and proteomic analyses suggested that PAT/Mix exerted its antitumor activity by silencing DEPDC1 mRNA in A549 cells,thereby influencing cellular processes and metabolic pathways.Additionally,PAT/Mix was found to promote the maturation of bone marrow dendritic cells(BMDCs),enhancing antigen processing and presentation.These findings indicated that PAT/Mix held promise as a therapeutic agent with both immunomodulatory and antitumor properties,owing not only to its peptide components but also to miRNAs,which played a critical therapeutic role.我国自古以来一直使用中药来治疗和预防疾病,包括中草药和动物药物,有研究表明中草药汤剂中的miRNA也是其发挥作用的关键成分之一。根据古书《本草突经》记载,猪脾是一种中药,煮熟后可食用,也可以用于中药组方。本研究针对主要由寡核苷酸和肽组成的新鲜猪脾提取液口服冻干粉PAT,以中性胞苷脂材DNCA和阳离子脂质CLD混合包载(PAT/Mix),发现其可以促进A549细胞的早期和晚期细胞凋亡,显著抑制A549和BCPAP细胞的增殖,瘤内注射可显著降低A549肺腺癌小鼠的肿瘤体积和重量。转录组学和蛋白质组学分析显示,PAT/Mix可能通过沉默A549细胞中的DEPDC1 m RNA进而影响细胞过程和代谢来发挥抗肿瘤生物活性,也能促进骨髓树突状细胞(BMDC)的成熟,有利于其对肿瘤抗原的加工和呈递。PAT/Mix有望成为一种同时具有免疫调节和抗肿瘤作用的药物。

关 键 词：Extract of pig spleen miRNA DNCA CLD Anti-tumor efficacy 

分 类 号：R963[医药卫生—微生物与生化药学]