Advances in Liposomal Interleukin and Liposomal Interleukin Gene Therapy for Cancer: A Comprehensive Review of Preclinical Studies.

IF 5.5 3区医学 Q1 PHARMACOLOGY & PHARMACY Pharmaceutics Pub Date : 2025-03-18 DOI:10.3390/pharmaceutics17030383

Eman A Kubbara, Ahmed Bolad, Husam Malibary

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Abstract

Background: 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.

Methods: 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".

Results: 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.

Conclusions: Utilizing immune-stimulatory ILs through advanced liposomal delivery and gene therapy establishes a strong foundation for advancing cancer immunotherapy.

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白细胞介素脂质体和白细胞介素基因治疗癌症的研究进展：临床前研究综述。

背景：临床前研究表明，脂质体白介素（IL）治疗在癌症治疗中具有相当大的前景。本文综述了脂质体IL包封的成就、挑战和未来潜力，重点是临床前研究。方法：使用PubMed和Web of Science数据库进行结构化搜索，使用以下搜索词和布尔运算符：（“脂质体白介素”或“脂质体白介素”）和（“基因治疗”或“基因传递”）和（“癌症”或“肿瘤”或“肿瘤”）和（“临床前研究”或“动物模型”或“体外研究”）。结果：脂质体IL-2制剂显著增强肿瘤部位的递送和滞留。重组人白细胞介素（rhIL-2）吸附在小脂质体（35-50 nm）上，可显著减少小鼠模型中的转移。肝转移模型表明，脂质体IL-2优于游离IL-2，通过增强免疫反应，特别是在肝脏中。局部给药策略，包括在犬肺转移瘤中雾化脂质体IL-2和在小鼠肉瘤模型中胸腔内给药，可以降低全身毒性，同时促进免疫激活和肿瘤消退。脂质体IL基因治疗，将细胞因子基因直接传递到肿瘤部位，是一个显著的进展。IL-2基因治疗联合其他细胞因子，包括IL-6或双链RNA佐剂，可协同增强巨噬细胞和t细胞的活化。脂质体IL-4， IL-6和IL-21治疗在各种肿瘤类型中显示出潜力。将脂质体IL-2与化疗或免疫药物配对可改善缓解和生存。创新的策略，包括聚乙二醇化和配体靶向系统，优化递送，释放和治疗结果。结论：通过先进的脂质体输送和基因治疗，利用免疫刺激il为推进癌症免疫治疗奠定了坚实的基础。

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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来源期刊

Pharmaceutics Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science

CiteScore

7.90

自引率

11.10%

发文量

2379

审稿时长

16.41 days

期刊介绍： Pharmaceutics (ISSN 1999-4923) is an open access journal which provides an advanced forum for the science and technology of pharmaceutics and biopharmaceutics. It publishes reviews, regular research papers, communications, and short notes. Covered topics include pharmacokinetics, toxicokinetics, pharmacodynamics, pharmacogenetics and pharmacogenomics, and pharmaceutical formulation. Our aim is to encourage scientists to publish their experimental and theoretical details in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.