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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

Damage-associated molecular pattern (DAMP) production by dying tumor cells induced by apoptotic pathway. (a) Expression of Hsp70 and Hsp90 on 2 h postirradiated cells, 16 h postirradiated cells, and bPEI-SPION 2 h postirradiated cells was measured by flow cytometry. Hsp70 and Hsp90 (shaded histogram) production compared with isotype controls (open histogram). 2 h postirradiated cells and bPEI-SPION 2 h postirradiated cells showed high percentage of positive cells on Hsp70 and Hsp90 expression. (b) Danger signal (Hsp70, Hsp90, and HMGB1) release from the cells was analyzed by Western blotting. bPEI-SPION 2 h postirradiated cells and 2 h postirradiated cells produced higher levels of the three danger signals compared with 16 h postirradiated cells. Data are representative of three independent experiments.
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fig3: Damage-associated molecular pattern (DAMP) production by dying tumor cells induced by apoptotic pathway. (a) Expression of Hsp70 and Hsp90 on 2 h postirradiated cells, 16 h postirradiated cells, and bPEI-SPION 2 h postirradiated cells was measured by flow cytometry. Hsp70 and Hsp90 (shaded histogram) production compared with isotype controls (open histogram). 2 h postirradiated cells and bPEI-SPION 2 h postirradiated cells showed high percentage of positive cells on Hsp70 and Hsp90 expression. (b) Danger signal (Hsp70, Hsp90, and HMGB1) release from the cells was analyzed by Western blotting. bPEI-SPION 2 h postirradiated cells and 2 h postirradiated cells produced higher levels of the three danger signals compared with 16 h postirradiated cells. Data are representative of three independent experiments.

Mentions: As expected, more than 90% of bPEI-SPION 2 h postirradiated cells expressed surface Hsp70 and Hsp90 (Figure 3(a)). Although 2 h postirradiated cells also showed a high percentage of Hsp70 and Hsp90 expression (Figure 3(a)), more than 60% of cells were viable (Figure 2(a)). Similarly, 16 h postirradiated cells presented high percentage of cells which were positive for these two markers. The environment in which antigens contact DCs can determine their activation status [15]. For this reason, the release of danger signals such as Hsp70, Hsp90, and HMGB1 was investigated by Western blotting. The 2 h postirradiated cells and bPEI-SPION 2 h postirradiated cells released higher levels of three danger signals compared to 16 h postirradiated cells (Figure 3(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)

Damage-associated molecular pattern (DAMP) production by dying tumor cells induced by apoptotic pathway. (a) Expression of Hsp70 and Hsp90 on 2 h postirradiated cells, 16 h postirradiated cells, and bPEI-SPION 2 h postirradiated cells was measured by flow cytometry. Hsp70 and Hsp90 (shaded histogram) production compared with isotype controls (open histogram). 2 h postirradiated cells and bPEI-SPION 2 h postirradiated cells showed high percentage of positive cells on Hsp70 and Hsp90 expression. (b) Danger signal (Hsp70, Hsp90, and HMGB1) release from the cells was analyzed by Western blotting. bPEI-SPION 2 h postirradiated cells and 2 h postirradiated cells produced higher levels of the three danger signals compared with 16 h postirradiated cells. Data are representative of three independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig3: Damage-associated molecular pattern (DAMP) production by dying tumor cells induced by apoptotic pathway. (a) Expression of Hsp70 and Hsp90 on 2 h postirradiated cells, 16 h postirradiated cells, and bPEI-SPION 2 h postirradiated cells was measured by flow cytometry. Hsp70 and Hsp90 (shaded histogram) production compared with isotype controls (open histogram). 2 h postirradiated cells and bPEI-SPION 2 h postirradiated cells showed high percentage of positive cells on Hsp70 and Hsp90 expression. (b) Danger signal (Hsp70, Hsp90, and HMGB1) release from the cells was analyzed by Western blotting. bPEI-SPION 2 h postirradiated cells and 2 h postirradiated cells produced higher levels of the three danger signals compared with 16 h postirradiated cells. Data are representative of three independent experiments.
Mentions: As expected, more than 90% of bPEI-SPION 2 h postirradiated cells expressed surface Hsp70 and Hsp90 (Figure 3(a)). Although 2 h postirradiated cells also showed a high percentage of Hsp70 and Hsp90 expression (Figure 3(a)), more than 60% of cells were viable (Figure 2(a)). Similarly, 16 h postirradiated cells presented high percentage of cells which were positive for these two markers. The environment in which antigens contact DCs can determine their activation status [15]. For this reason, the release of danger signals such as Hsp70, Hsp90, and HMGB1 was investigated by Western blotting. The 2 h postirradiated cells and bPEI-SPION 2 h postirradiated cells released higher levels of three danger signals compared to 16 h postirradiated cells (Figure 3(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