Journal article
Characterization of CPH:SA microparticle-based delivery of interleukin-1 alpha for cancer immunotherapy
Bioengineering & translational medicine, Vol.8(3), e10465
05/2023
DOI: 10.1002/btm2.10465
PMCID: PMC10189482
PMID: 37206237
Abstract
Background: Interleukin-1 alpha (IL-1 alpha) is a pro-inflammatory cytokine that can activate immune effector cells and trigger anti-tumor immune responses. However, dose-limiting toxicities including cytokine storm and hypotension has limited its use in the clinic as a cancer therapy. We propose that polymeric microparticle (MP)-based delivery of IL-1 alpha will suppress the acute pro-inflammatory side effects by allowing for slow and controlled release of IL-1 alpha systemically, while simultaneously triggering an anti-tumor immune response. Methods: Polyanhydride copolymers composed of 1,6-bis-(p-carboxyphenoxy)-hexane:sebacic 20:80 (CPH:SA 20:80) was utilized to fabricate MPs. Recombinant IL-1 alpha (rIL-1 alpha) was encapsulated into CPH:SA 20:80 MPs (IL-1 alpha-MPs) and the MPs were characterized by size, charge, loading efficiency, and in-vitro release and activity of IL-1 alpha. IL-1 alpha-MPs were injected intraperitonially into head and neck squamous cell carcinoma (HNSCC)-bearing C57Bl/6 mice and monitored for changes in weight, tumor growth, circulating cytokines/chemokines, hepatic and kidney enzymes, blood pressure, heart rate, and tumor-infiltrating immune cells. Results: CPH:SA IL-1 alpha-MPs demonstrated sustained release kinetics of IL-1 alpha (100% protein released over 8-10 days) accompanied by minimal weight loss and systemic inflammation compared to rIL-1 alpha-treated mice. Blood pressure measured by radiotelemetry in conscious mice demonstrates that rIL-1 alpha-induced hypotension was prevented in IL-1 alpha-MP-treated mice. Liver and kidney enzymes were within normal range for all control and cytokine-treated mice. Both rIL-1 alpha and IL-1 alpha-MP-treated mice showed similar delays in tumor growth and similar increases in tumor-infiltrating CD3+ T cells, macrophages, and dendritic cells. Conclusions: CPH:SA-based IL-1 alpha-MPs generated a slow and sustained systemic release of IL-1 alpha resulting in reduced weight loss, systemic inflammation, and hypotension accompanied by an adequate anti-tumor immune response in HNSCC-tumor bearing mice. Therefore, MPs based on CPH:SA formulations may be promising as delivery vehicles for IL-1 alpha to achieve safe, effective, and durable antitumor responses for HNSCC patients.
Details
- Title: Subtitle
- Characterization of CPH:SA microparticle-based delivery of interleukin-1 alpha for cancer immunotherapy
- Creators
- M. M. Hasibuzzaman - University of IowaRui He - University of IowaIshrat Nourin Khan - University of IowaRasna Sabharwal - University of IowaAliasger K. K. Salem - University of IowaAndrean Llewela Simons-Burnett - Univ Iowa, Interdisciplinary Grad Program Human Toxicol, Iowa City, IA USA
- Resource Type
- Journal article
- Publication Details
- Bioengineering & translational medicine, Vol.8(3), e10465
- DOI
- 10.1002/btm2.10465
- PMID
- 37206237
- PMCID
- PMC10189482
- NLM abbreviation
- Bioeng Transl Med
- ISSN
- 2380-6761
- eISSN
- 2380-6761
- Publisher
- Wiley
- Number of pages
- 13
- Grant note
- HL149677 / National Heart, Lung, and Blood Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) AG070188 / National Institute on Aging; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) BX004829 / U.S. Department of VeteransAffairs; US Department of Veterans Affairs
- Language
- English
- Electronic publication date
- 12/07/2022
- Date published
- 05/2023
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Oral Pathology, Radiology and Medicine; Pathology; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Cardiovascular Medicine; Orthopedics and Rehabilitation; Radiation Oncology; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering; Internal Medicine
- Record Identifier
- 9984355759702771
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