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
{"title":"用于联合递送 STAT3 siRNA 脂质体和盐酸利多卡因的免疫治疗水凝胶,可一次性用于 NSCLC 术后综合治疗","authors":"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","doi":"10.1016/j.ajps.2024.100925","DOIUrl":null,"url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":10.7000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000424/pdfft?md5=af9866fa79376685878ba98645ec3d3b&pid=1-s2.0-S1818087624000424-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Immunotherapeutic hydrogel for co-delivery of STAT3 siRNA liposomes and lidocaine hydrochloride for postoperative comprehensive management of NSCLC in a single application\",\"authors\":\"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\",\"doi\":\"10.1016/j.ajps.2024.100925\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>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.</p></div>\",\"PeriodicalId\":8539,\"journal\":{\"name\":\"Asian Journal of Pharmaceutical Sciences\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":10.7000,\"publicationDate\":\"2024-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S1818087624000424/pdfft?md5=af9866fa79376685878ba98645ec3d3b&pid=1-s2.0-S1818087624000424-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Asian Journal of Pharmaceutical Sciences\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1818087624000424\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Asian Journal of Pharmaceutical Sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1818087624000424","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Immunotherapeutic hydrogel for co-delivery of STAT3 siRNA liposomes and lidocaine hydrochloride for postoperative comprehensive management of NSCLC in a single application
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.
期刊介绍:
The Asian Journal of Pharmaceutical Sciences (AJPS) serves as the official journal of the Asian Federation for Pharmaceutical Sciences (AFPS). Recognized by the Science Citation Index Expanded (SCIE), AJPS offers a platform for the reporting of advancements, production methodologies, technologies, initiatives, and the practical application of scientific knowledge in the field of pharmaceutics. The journal covers a wide range of topics including but not limited to controlled drug release systems, drug targeting, physical pharmacy, pharmacodynamics, pharmacokinetics, pharmacogenomics, biopharmaceutics, drug and prodrug design, pharmaceutical analysis, drug stability, quality control, pharmaceutical engineering, and material sciences.