尽管非小细胞肺癌（NSCLC）的标准治疗是手术切除，但癌症复发和并发症，例如诱发恶性胸腔积液（MPE）和明显的术后疼痛，通常会导致治疗失败。在这项研究中，开发了一种基于藻酸盐的混合水凝胶（SOG），可以在手术期间注射到肺部的切除表面。简而言之，将预先装载有信号转导器和转录激活剂 3 (STAT3) 小干扰 RNA 和盐酸利多卡因的内质网修饰脂质体 (MSL) 封装在 SOG 中。一旦应用，MSL 就会强烈下调肿瘤微环境中 STAT3 的表达，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（LID）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，包括减少原位 NSCLC 小鼠模型中的 MPE 体积和缓解疼痛，即使单次给药也是如此。 MSL@LID@SOG 显示出对 NSCLC 肿瘤切除进行综合临床管理的潜力，并可能改变其他癌症的治疗模式。© 2024 沉阳药科大学。由 Elsevier B.V. 出版

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.© 2024 Shenyang Pharmaceutical University. Published by Elsevier B.V.