Immunotherapeutic hydrogel for co-delivery of STAT3 siRNA liposomes and lidocaine hydrochloride for postoperative comprehensive management of NSCLC in a single application  

作　　者：Xianglei Fu Yanbin Shi Zili Gu Hengchang Zang Lian Li Qingjie Wang Yongjun Wang Xiaogang Zhao Hang Wu Shengnan Qiu Yankun Zhang Jiamin Zhou Xiangqin Chen Hua Shen Guimei Lin 

机构地区：[1]Department of Pharmaceutics,School of Pharmaceutical Sciences,Cheeloo College of Medicine,Shandong University,Jinan 250012,China [2]School of Mechanical and Automotive Engineering,Qilu University of Technology(Shandong Academy of Sciences),Jinan 250353,China [3]Department of Radiology,Leiden University Medical Center,Albinusdreef 2,2333 ZA Leiden,Netherlands [4]NMPA Key Laboratory for Technology Research and Evaluation of Drug Products,School of Pharmaceutical Sciences,Cheeloo College of Medicine,Shandong University,Jinan 250012,China [5]Laboratory of Basic Medical Sciences,Qilu Hospital,Shandong University,Jinan 250063,China [6]Wuya College of Innovation,Shenyang Pharmaceutical University,Shenyang 110016,China [7]Department of Thoracic Surgery,The Second Hospital of Shandong University,Jinan 250033,China

出　　处：《Asian Journal of Pharmaceutical Sciences》2024年第3期115-130,共16页亚洲药物制剂科学（英文）

基　　金：supported by the National Natural Science Foundation of China[grant numbers 21873057,22373059];the Natural Science Foundation of Shandong Province[grant numbers ZR2023MB082]。

摘　　要：Despite standard treatment for non-small cell lung cancer(NSCLC)being surgical resection,cancer recurrence and complications,such as induction of malignant pleural effusion(MPE)and significant postoperative pain,usually result in treatment failure.In this study,an alginate-based hybrid hydrogel(SOG)is developed that can be injected into the resection surface of the lungs during surgery.Briefly,endoplasmic reticulum-modified liposomes(MSLs)pre-loaded with the signal transducer and activator of transcription 3(STAT3)small interfering RNA and lidocaine hydrochloride are encapsulated in SOG.Once applied,MSLs strongly downregulated STAT3 expression in the tumor microenvironment,resulting in the apoptosis of lung cancer cells and polarization of tumor-associated macrophages towards the M1-like phenotype.Meanwhile,the release of lidocaine hydrochloride(LID)was beneficial for pain relief and natural killer cell activation.Our data demonstrated MSL@LID@SOG not only efficiently inhibited tumor growth but also potently improved the quality of life,including reduced MPE volume and pain relief in orthotopic NSCLC mouse models,even with a single administration.MSL@LID@SOG shows potential for comprehensive clinical management upon tumor resection in NSCLC,and may alter the treatment paradigms for other cancers.

关 键 词：LIPOSOME HYDROGEL Signal transducer and activator of transcription 3 Non-small cell lung cancer MACROPHAGE 

分 类 号：R943[医药卫生—药剂学]