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

IF 10.7 1区 医学 Q1 PHARMACOLOGY & PHARMACY Asian Journal of Pharmaceutical Sciences Pub Date : 2024-06-01 DOI:10.1016/j.ajps.2024.100925
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
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引用次数: 0

摘要

尽管非小细胞肺癌(NSCLC)的标准治疗方法是手术切除,但癌症复发和并发症(如诱发恶性胸腔积液和明显的术后疼痛)通常会导致治疗失败。本研究开发了一种基于藻酸盐的混合水凝胶(SOG),可在手术中注入肺部切除面。简而言之,内质网修饰的脂质体(MSL)预载了信号转导子和转录激活子 3(STAT3)小干扰 RNA 和盐酸利多卡因,被包裹在 SOG 中。应用 MSLs 后,STAT3 在肿瘤微环境中的表达被强烈下调,导致肺癌细胞凋亡和肿瘤相关巨噬细胞向 M1 样表型极化。同时,盐酸利多卡因的释放有利于缓解疼痛和激活自然杀伤细胞。我们的数据表明,MSL@LID@SOG 不仅能有效抑制肿瘤生长,还能有效改善生活质量,包括减少 MPE 体积和缓解正位 NSCLC 小鼠模型的疼痛,即使单次给药也是如此。MSL@LID@SOG显示了在NSCLC肿瘤切除后进行综合临床治疗的潜力,并可能改变其他癌症的治疗模式。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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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.

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来源期刊
Asian Journal of Pharmaceutical Sciences
Asian Journal of Pharmaceutical Sciences Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
18.30
自引率
2.90%
发文量
11
审稿时长
14 days
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.
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