Kubbara Eman A, Bolad Ahmed, Malibary Husam
Clinical Biochemistry Department, Faculty of Medicine, Rabigh Branch, King Abdulaziz University, Rabigh 21911, Saudi Arabia.
Department of Biochemistry and Molecular Biology, Faculty of Medicine, Al-Neelain University, Khartoum 11121, Sudan.
Pharmaceutics. 2025 Mar 18;17(3):383. doi: 10.3390/pharmaceutics17030383.
Preclinical studies on liposomal interleukin (IL) therapy demonstrate considerable promise in cancer treatment. This review explores the achievements, challenges, and future potential of liposomal IL encapsulation, focusing on preclinical studies.
A structured search was conducted using the PubMed and Web of Science databases with the following search terms and Boolean operators: ("liposomal interleukin" OR "liposome-encapsulated interleukin") AND ("gene therapy" OR "gene delivery") AND ("cancer" OR "tumor" OR "oncology") AND ("pre-clinical studies" OR "animal models" OR "in vitro studies".
Liposomal IL-2 formulations are notable for enhancing delivery and retention at tumor sites. Recombinant human interleukin (rhIL-2) adsorbed onto small liposomes (35-50 nm) substantially reduces metastases in murine models. Hepatic metastasis models demonstrate superior efficacy of liposomal IL-2 over free IL-2 by enhancing immune responses, particularly in the liver. Localized delivery strategies, including nebulized liposomal IL-2 in canine pulmonary metastases and intrathoracic administration in murine sarcoma models, reduce systemic toxicity while promoting immune activation and tumor regression. Liposomal IL gene therapy, delivering cytokine genes directly to tumor sites, represents a notable advancement. Combining IL-2 gene therapy with other cytokines, including IL-6 or double-stranded RNA adjuvants, synergistically enhances macrophage and T-cell activation. Liposomal IL-4, IL-6, and IL-21 therapies show potential across various tumor types. Pairing liposomal IL-2 with chemotherapy or immune agents improves remission and survival. Innovative strategies, including PEGylation and ligand-targeted systems, optimize delivery, release, and therapeutic outcomes.
Utilizing immune-stimulatory ILs through advanced liposomal delivery and gene therapy establishes a strong foundation for advancing cancer immunotherapy.
脂质体白细胞介素（IL）疗法的临床前研究在癌症治疗中显示出巨大潜力。本综述探讨脂质体包裹IL的成果、挑战及未来潜力，重点关注临床前研究。
使用PubMed和Web of Science数据库进行结构化检索，检索词及布尔运算符如下：（“脂质体白细胞介素”或“脂质体包裹的白细胞介素”）与（“基因疗法”或“基因递送”）与（“癌症”或“肿瘤”或“肿瘤学”）与（“临床前研究”或“动物模型”或“体外研究”）。
脂质体IL-2制剂在增强肿瘤部位的递送和滞留方面表现突出。吸附在小脂质体（35 - 50纳米）上的重组人白细胞介素（rhIL-2）可大幅减少小鼠模型中的转移。肝转移模型显示，脂质体IL-2通过增强免疫反应，尤其是在肝脏中的免疫反应，比游离IL-2具有更高的疗效。局部递送策略，包括犬肺转移模型中雾化脂质体IL-2和小鼠肉瘤模型中的胸腔内给药，可降低全身毒性，同时促进免疫激活和肿瘤消退。脂质体IL基因疗法将细胞因子基因直接递送至肿瘤部位，是一项显著进展。将IL-2基因疗法与其他细胞因子（包括IL-6或双链RNA佐剂）联合使用，可协同增强巨噬细胞和T细胞的激活。脂质体IL-4、IL-6和IL-21疗法在多种肿瘤类型中均显示出潜力。将脂质体IL-2与化疗或免疫药物联合使用可改善缓解率和生存率。包括聚乙二醇化和配体靶向系统在内的创新策略可优化递送、释放和治疗效果。
通过先进的脂质体递送和基因疗法利用免疫刺激IL，为推进癌症免疫疗法奠定了坚实基础。
