Journal article
Evaluation of the In vivo Antitumor Activity of Polyanhydride IL-1α Nanoparticles
Journal of Visualized Experiments, Vol.172, e62683
06/28/2021
DOI: 10.3791/62683
Abstract
Cytokine therapy is a promising immunotherapeutic strategy that can produce robust antitumor immune responses in cancer patients. The proinflammatory cytokine interleukin-1 alpha (IL-1α) has been evaluated as an anticancer agent in several preclinical and clinical studies. However, dose-limiting toxicities, including flu-like symptoms and hypotension, have dampened the enthusiasm for this therapeutic strategy. Polyanhydride nanoparticle (NP)-based delivery of IL-1α would represent an effective approach in this context since this may allow for a slow and controlled release of IL-1α systemically while reducing toxic side effects. Here an analysis of the antitumor activity of IL-1α-loaded polyanhydride NPs in a head and neck squamous cell carcinoma (HNSCC) syngeneic mouse model is described. Murine oropharyngeal epithelial cells stably expressing HPV16 E6/E7 together with hRAS and luciferase (mEERL) cells were injected subcutaneously into the right flank of C57BL/6J mice. Once tumors reached 3-4 mm in any direction, a 1.5% IL-1a - loaded 20:80 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane:1,6-bis(p-carboxyphenoxy)hexane (CPTEG: CPH) nanoparticle (IL-1α-NP) formulation was administered to mice intraperitoneally. Tumor size and body weight were continuously measured until tumor size or weight loss reached euthanasia criteria. Blood samples were taken to evaluate antitumor immune responses by submandibular venipuncture, and inflammatory cytokines were measured through cytokine multiplex assays. Tumor and inguinal lymph nodes were resected and homogenized into a single-cell suspension to analyze various immune cells through multicolor flow cytometry. These standard methods will allow investigators to study the antitumor immune response and potential mechanism of immunostimulatory NPs and other immunotherapy agents for cancer treatment.
Details
- Title: Subtitle
- Evaluation of the In vivo Antitumor Activity of Polyanhydride IL-1α Nanoparticles
- Creators
- M. M Hasibuzzaman - University of IowaKathleen A Ross - Iowa State UniversityAliasger K Salem - Iowa State UniversityBalaji Narasimhan - Iowa State UniversityAndrean L Simons - Iowa State University
- Resource Type
- Journal article
- Publication Details
- Journal of Visualized Experiments, Vol.172, e62683
- DOI
- 10.3791/62683
- ISSN
- 1940-087X
- eISSN
- 1940-087X
- Language
- English
- Date published
- 06/28/2021
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Oral Pathology, Radiology and Medicine; Pathology; Pharmaceutical Sciences and Experimental Therapeutics; Orthopedics and Rehabilitation; Radiation Oncology; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering
- Record Identifier
- 9984186529002771
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