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Branched Polyethylenimine-Superparamagnetic Iron Oxide Nanoparticles (bPEI-SPIONs) Improve the Immunogenicity of Tumor Antigens and Enhance Th1 Polarization of Dendritic Cells.

Hoang MD, Lee HJ, Lee HJ, Jung SH, Choi NR, Vo MC, Nguyen-Pham TN, Kim HJ, Park IK, Lee JJ - J Immunol Res (2015)

Bottom Line: Nanoparticles in the field of dendritic cell (DC) research are emerging as a promising method of enhancing the efficacy of cancer immunotherapy.The 2 h postirradiated cells and bPEI-SPION 2 h postirradiated cells released immunogenic proteins, including Hsp70, Hsp90, and HMGB1.The DCs loaded with bPEI-SPION 2 h postirradiated cells showed the highest IL-12p70 production and Th1 polarization compared with other DCs.

View Article: PubMed Central - PubMed

Affiliation: Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo 519-763, Republic of Korea ; Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo 519-763, Republic of Korea.

ABSTRACT
Nanoparticles in the field of dendritic cell (DC) research are emerging as a promising method of enhancing the efficacy of cancer immunotherapy. We investigated the effect of branched polyethylenimine-superparamagnetic iron oxide nanoparticles (bPEI-SPIONs) on tumor cells loaded onto DCs. The tumor antigens were prepared as follows: (1) apoptotic U266 cells with ultraviolet B (UVB) irradiation followed by a 2 h incubation in the absence (2 h postirradiated cells) or (2) presence of bPEI-SPIONs (bPEI-SPION 2 h postirradiated cells) and (3) apoptotic U266 cells with UVB irradiation followed by an overnight 16 h incubation (16 h postirradiated cells). bPEI-SPIONs render U266 cells sensitive to UVB irradiation through reactive oxygen species production to accelerate apoptotic death. The 2 h postirradiated cells and bPEI-SPION 2 h postirradiated cells released immunogenic proteins, including Hsp70, Hsp90, and HMGB1. The DCs loaded with bPEI-SPION 2 h postirradiated cells showed the highest IL-12p70 production and Th1 polarization compared with other DCs. These results suggest that bPEI-SPIONs are a promising method of enhancing the immunogenicity of tumor cells and promoting Th1 polarization of DCs loaded with these tumor cells.

No MeSH data available.


Related in: MedlinePlus

T cell polarization of DCs. Intracellular IFN-γ and IL-4 levels were measured using flow cytometry. bPEI-SPIONs 2 h postirradiated DCs exhibited the highest Th1 response (IL4−IFNγ+) up to 18% of total T cells. (b) Amount of secreted IFN-γ and IL-4 was measured by ELISA. T cells polarized by bPEI-SPION 2 h postirradiated DCs presented a significant increase level of IFN-γ. Data are representative of three independent experiments (∗P < 0.05).
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fig5: T cell polarization of DCs. Intracellular IFN-γ and IL-4 levels were measured using flow cytometry. bPEI-SPIONs 2 h postirradiated DCs exhibited the highest Th1 response (IL4−IFNγ+) up to 18% of total T cells. (b) Amount of secreted IFN-γ and IL-4 was measured by ELISA. T cells polarized by bPEI-SPION 2 h postirradiated DCs presented a significant increase level of IFN-γ. Data are representative of three independent experiments (∗P < 0.05).

Mentions: Although danger signals were released in antigen (2 h postirradiated cells and bPEI-SPION 2 h postirradiated cells) contact milieu, surface maturation-marker expression by 2 h postirradiated DCs and bPEI-SPION 2 h postirradiated DCs was similar to that by 16 h postirradiated DCs (Figure 4(a)). In addition, there were no differences in antigen uptake and migration toward CCL21 among the groups (Figures 4(b) and 4(c)). Interestingly, 2 h postirradiated DCs and bPEI-SPION 2 h postirradiated DCs showed a significant increase in IL-12p70 production but unchanged IL-10 levels, compared with 16 h postirradiated DCs (Figure 4(d)). IL-23 production by the three types of DCs was similar (data not shown). Based on evaluation of T cell polarization by intracellular cytokine staining, bPEI-SPION 2 h postirradiated DCs showed the strongest expression of the Th1 polarizing cytokine, IFN-γ, reaching 18% of total analyzed T cells (Figure 5(a)). Although the IL-12p70 level produced by 2 h postirradiated DCs was higher than that by 16 h postirradiated DCs, Th1 polarization capacity was slightly increased in 2 h postirradiated DCs compared to 16 h postirradiated DCs. Besides, amount of released IFN-γ and IL-4 was measured by ELISA and we observed a significant increase of IFN-γ in T cells polarized by bPEI-SPION 2 h postirradiated DCs (Figure 5(b)).


Branched Polyethylenimine-Superparamagnetic Iron Oxide Nanoparticles (bPEI-SPIONs) Improve the Immunogenicity of Tumor Antigens and Enhance Th1 Polarization of Dendritic Cells.

Hoang MD, Lee HJ, Lee HJ, Jung SH, Choi NR, Vo MC, Nguyen-Pham TN, Kim HJ, Park IK, Lee JJ - J Immunol Res (2015)

T cell polarization of DCs. Intracellular IFN-γ and IL-4 levels were measured using flow cytometry. bPEI-SPIONs 2 h postirradiated DCs exhibited the highest Th1 response (IL4−IFNγ+) up to 18% of total T cells. (b) Amount of secreted IFN-γ and IL-4 was measured by ELISA. T cells polarized by bPEI-SPION 2 h postirradiated DCs presented a significant increase level of IFN-γ. Data are representative of three independent experiments (∗P < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4499411&req=5

fig5: T cell polarization of DCs. Intracellular IFN-γ and IL-4 levels were measured using flow cytometry. bPEI-SPIONs 2 h postirradiated DCs exhibited the highest Th1 response (IL4−IFNγ+) up to 18% of total T cells. (b) Amount of secreted IFN-γ and IL-4 was measured by ELISA. T cells polarized by bPEI-SPION 2 h postirradiated DCs presented a significant increase level of IFN-γ. Data are representative of three independent experiments (∗P < 0.05).
Mentions: Although danger signals were released in antigen (2 h postirradiated cells and bPEI-SPION 2 h postirradiated cells) contact milieu, surface maturation-marker expression by 2 h postirradiated DCs and bPEI-SPION 2 h postirradiated DCs was similar to that by 16 h postirradiated DCs (Figure 4(a)). In addition, there were no differences in antigen uptake and migration toward CCL21 among the groups (Figures 4(b) and 4(c)). Interestingly, 2 h postirradiated DCs and bPEI-SPION 2 h postirradiated DCs showed a significant increase in IL-12p70 production but unchanged IL-10 levels, compared with 16 h postirradiated DCs (Figure 4(d)). IL-23 production by the three types of DCs was similar (data not shown). Based on evaluation of T cell polarization by intracellular cytokine staining, bPEI-SPION 2 h postirradiated DCs showed the strongest expression of the Th1 polarizing cytokine, IFN-γ, reaching 18% of total analyzed T cells (Figure 5(a)). Although the IL-12p70 level produced by 2 h postirradiated DCs was higher than that by 16 h postirradiated DCs, Th1 polarization capacity was slightly increased in 2 h postirradiated DCs compared to 16 h postirradiated DCs. Besides, amount of released IFN-γ and IL-4 was measured by ELISA and we observed a significant increase of IFN-γ in T cells polarized by bPEI-SPION 2 h postirradiated DCs (Figure 5(b)).

Bottom Line: Nanoparticles in the field of dendritic cell (DC) research are emerging as a promising method of enhancing the efficacy of cancer immunotherapy.The 2 h postirradiated cells and bPEI-SPION 2 h postirradiated cells released immunogenic proteins, including Hsp70, Hsp90, and HMGB1.The DCs loaded with bPEI-SPION 2 h postirradiated cells showed the highest IL-12p70 production and Th1 polarization compared with other DCs.

View Article: PubMed Central - PubMed

Affiliation: Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo 519-763, Republic of Korea ; Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo 519-763, Republic of Korea.

ABSTRACT
Nanoparticles in the field of dendritic cell (DC) research are emerging as a promising method of enhancing the efficacy of cancer immunotherapy. We investigated the effect of branched polyethylenimine-superparamagnetic iron oxide nanoparticles (bPEI-SPIONs) on tumor cells loaded onto DCs. The tumor antigens were prepared as follows: (1) apoptotic U266 cells with ultraviolet B (UVB) irradiation followed by a 2 h incubation in the absence (2 h postirradiated cells) or (2) presence of bPEI-SPIONs (bPEI-SPION 2 h postirradiated cells) and (3) apoptotic U266 cells with UVB irradiation followed by an overnight 16 h incubation (16 h postirradiated cells). bPEI-SPIONs render U266 cells sensitive to UVB irradiation through reactive oxygen species production to accelerate apoptotic death. The 2 h postirradiated cells and bPEI-SPION 2 h postirradiated cells released immunogenic proteins, including Hsp70, Hsp90, and HMGB1. The DCs loaded with bPEI-SPION 2 h postirradiated cells showed the highest IL-12p70 production and Th1 polarization compared with other DCs. These results suggest that bPEI-SPIONs are a promising method of enhancing the immunogenicity of tumor cells and promoting Th1 polarization of DCs loaded with these tumor cells.

No MeSH data available.


Related in: MedlinePlus