Polyethyleneimine modification of aluminum hydroxide nanoparticle enhances antigen transportation and cross-presentation of dendritic cells.
Int J Nanomedicine
Aluminum Hydroxide; Animals; Antigen Presentation; Antigens, Neoplasm; Cancer Vaccines; Cross-Priming; Dendritic Cells; Humans; Immunotherapy; Mice, Inbred C57BL; Nanoparticles; Ovalbumin; Polyethyleneimine; T-Lymphocytes
Background: The aim of this study was to explore the feasibility of delivering tumor antigens and enhancing the antigen cross-presentation of dendritic cells (DCs) by aluminum hydroxide nanoparticle with polyethyleneimine (PEI) modification (LV@HPA/PEI).
Materials and methods: The LV@HPA nanoparticles were modified by PEI first, then the influence of LV@HPA/PEI on DCs was examined. The distinct expression of ovalbumin (OVA) protein transported into DCs by LV@HPA/PEI was observed by flow cytometry and Western blot. The biocompatibility of LV@HPA/PEI, maturity and antigen cross-presentation of DCs was observed in vitro. Tumor derived autophagosomes (DRibbles) combined with LV@HPA/PEI were loaded into DCs, and DC vaccines were used to immunize mice. The percentage of CD3
Results: In our study, we described how LV@HPA/PEI can be a functionalized antigen delivery system with notable antigen transport effect and negligible cytotoxicity. It was found that LV@HPA/PEI could be easily internalized into DCs to assist antigen release into the cytoplasm. In addition, DCs matured gradually after loading with LV@HPA/PEI-OVA, which increased significantly the cytokine IL-12 secretion and expression of surface molecules CD80 and CD86. Interestingly, DCs loaded with LV@HPA/PEI-DRibbles could promote the activation of tumor-specific T cells both in murine and in human T cells. In the following in vivo experiments, the vaccine of LV@HPA/PEI-DRibble-DCs significantly inhibited tumor growth and improved the survival rate of the PancO2 tumor-bearing mice.
Conclusion: We established a high-performance anti-tumor vaccine of DCs loaded with LV@ HPA/PEI nanoparticles and tumor-associated antigens in autophagosomes (DRibbles), which could serve as a therapeutic strategy in cancer immunotherapy.
Earle A. Chiles Research Institute
Dong, Heng; Wen, Zhi-Fa; Chen, Lin; Zhou, Na; Liu, Hui; Dong, Shiling; Hu, Hong-Ming; and Mou, Yongbin, "Polyethyleneimine modification of aluminum hydroxide nanoparticle enhances antigen transportation and cross-presentation of dendritic cells." (2018). Articles, Abstracts, and Reports. 183.