Polyethyleneimine modification of aluminum hydroxide nanoparticle enhances antigen transportation and cross-presentation of dendritic cells

Abstract

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 ( [email protected] /PEI). Materials and methods: The [email protected] nanoparticles were modified by PEI first, then the influence of [email protected] /PEI on DCs was examined. The distinct expression of ovalbumin (OVA) protein transported into DCs by [email protected] /PEI was observed by flow cytometry and Western blot. The biocompatibility of [email protected] /PEI, maturity and antigen cross-presentation of DCs was observed in vitro. Tumor derived autophagosomes (DRibbles) combined with [email protected] /PEI were loaded into DCs, and DC vaccines were used to immunize mice. The percentage of CD3 + CD8 + IFN-γ + T cells in immunized mice was determined by flow cytometry. Additionally, the functional properties of the [email protected] /PEI-DRibble-DCs vaccine were examined in vivo in PancO2 tumor-bearing mice. Results: In our study, we described how [email protected] /PEI can be a functionalized antigen delivery system with notable antigen transport effect and negligible cytotoxicity. It was found that [email protected] /PEI could be easily internalized into DCs to assist antigen release into the cytoplasm. In addition, DCs matured gradually after loading with [email protected] /PEI-OVA, which increased significantly the cytokine IL-12 secretion and expression of surface molecules CD80 and CD86. Interestingly, DCs loaded with [email protected] /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 [email protected] /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 [email protected] /PEI nanoparticles and tumor-associated antigens in autophagosomes (DRibbles), which could serve as a therapeutic strategy in cancer immunotherapy. Keywords: aluminum hydroxide, antigen delivery, DRibbles, nano-adjuvant, cancer immunotherapy, autophagosome