Abstract
Purpose
The invention and application of new immunotherapeutic methods can compensate for the inefficiency of conventional cancer treatment approaches, partly due to the inhibitory microenvironment of the tumor. In this study, we tried to inhibit the growth of cancer cells and induce anti-tumor immune responses by silencing the expression of the β-catenin in the tumor microenvironment and transmitting interleukin (IL)-15 cytokine to provide optimal conditions for the dendritic cell (DC) vaccine.
Methods
For this purpose, we used folic acid (FA)-conjugated SPION-carboxymethyl dextran (CMD) chitosan (C) nanoparticles (NPs) to deliver anti-β-catenin siRNA and IL-15 to cancer cells.
Results
The results showed that the codelivery of β-catenin siRNA and IL-15 significantly reduced the growth of cancer cells and increased the immune response. The treatment also considerably stimulated the performance of the DC vaccine in triggering anti-tumor immunity, which inhibited tumor development and increased survival in mice in two different cancer models.
Conclusions
These findings suggest that the use of new nanocarriers such as SPION-C-CMD-FA could be an effective way to use as a novel combination therapy consisting of β-catenin siRNA, IL-15, and DC vaccine to treat cancer.
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Data Availability
The data supporting this study’s findings are available from the corresponding author upon reasonable request.
Change history
07 December 2022
This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1007/s11095-022-03456-y
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Contributions
Armin Mahmoud Salehi Kheshti: Conceptualization; Methodology; Data curation; Writing – review & editing. Farnaz Hajizadeh:Writing Original draft, Conceptualization; Methodology. Asal Barshidi: Methodology. Bentolhoda Rashidi: Methodology; Data curation. Farbod Ebrahimi: Methodology. Simin Bahmanpour: review & editing. Vahid Karpisheh: Methodology; Formal analysis. Fatemeh Karimian Noukabadi: review & editing. Fariba Karoon Kiani: review & editing. Hadi Hassannia: Methodology. Fatemeh Atyabi: Methodology. Seyed Hossein Kiaie: Methodology; Data curation. Fatah Kashanchi: review & editing. Jamshid Gholizadeh Navashenaq: review & editing. Hamed Mohammadi: review & editing. Rafieh Bagherifar: review & editing. Reza Jafari: Methodology; Data curation. Naime Majidi Zolbanin: Conceptualization; Supervision; Writing–review &; editing; Correspondence. Farhad Jadidi-Niaragh: Conceptualization; Supervision; Writing–review & editing; Correspondence; Project administration.
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Figure S1
Validation of FA-C-CMD-SPION NPs. While the NPs were about 161 nm in size with a PDI of about 0.37 (a), they showed a zeta potential of about 9.2 mV (b). FTIR spectra demonstrate the proper formation of NPs (c). NPs had a regular spherical shape as investigated by SEM microscopy (d). TEM(e). NPs (1 ml at a concentration of 5 mg /ml) showed a high capacity to contain siRNA molecules so that they could load up to 20 μg of siRNA (Lane 1: naked siRNA, Lane 2: 5 μg, Lane 3: 10 μg, Lane 4: 15 μg, Lane 5: 20 μg of siRNA) (f). Evaluation of the stability of NPs in the serum environment showed their high ability to preserve the loaded contents (g). The release pattern of siRNA and IL-15 cytokine from NPs at two different pH values was investigated by spectroscopy and BCA protein measurement kit, respectively (h). (Folate–chitosan conjugate and carboxymethyl dextran (CMD) coated the SPIONs core). (JPG 2114 kb)
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Kheshti, A.M.S., Hajizadeh, F., Barshidi, A. et al. RETRACTED ARTICLE: Combination Cancer Immunotherapy with Dendritic Cell Vaccine and Nanoparticles Loaded with Interleukin-15 and Anti-beta-catenin siRNA Significantly Inhibits Cancer Growth and Induces Anti-Tumor Immune Response. Pharm Res 39, 353–367 (2022). https://doi.org/10.1007/s11095-022-03169-2
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DOI: https://doi.org/10.1007/s11095-022-03169-2