{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T21:29:57Z","timestamp":1782509397219,"version":"3.54.5"},"reference-count":213,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T00:00:00Z","timestamp":1742256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>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: (\u201cliposomal interleukin\u201d OR \u201cliposome-encapsulated interleukin\u201d) AND (\u201cgene therapy\u201d OR \u201cgene delivery\u201d) AND (\u201ccancer\u201d OR \u201ctumor\u201d OR \u201concology\u201d) AND (\u201cpre-clinical studies\u201d OR \u201canimal models\u201d OR \u201cin vitro studies\u201d. 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\u201350 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.<\/jats:p>","DOI":"10.3390\/pharmaceutics17030383","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T04:34:43Z","timestamp":1742272483000},"page":"383","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Advances in Liposomal Interleukin and Liposomal Interleukin Gene Therapy for Cancer: A Comprehensive Review of Preclinical Studies"],"prefix":"10.3390","volume":"17","author":[{"given":"Eman A.","family":"Kubbara","sequence":"first","affiliation":[{"name":"Clinical Biochemistry Department, Faculty of Medicine, Rabigh Branch, King Abdulaziz University, Rabigh 21911, Saudi Arabia"},{"name":"Department of Biochemistry and Molecular Biology, Faculty of Medicine, Al-Neelain University, Khartoum 11121, Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Bolad","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Unit of Immunology, Faculty of Medicine, Al-Neelain University, Khartoum 11121, Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1314-8031","authenticated-orcid":false,"given":"Husam","family":"Malibary","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, King Abdulaziz University, Rabigh 21911, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. 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