| Autor: |
Yuba E; Department of Applied Chemistry, Graduate School of Engineering, Osaka Metropolitan University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 5998531, Japan. yuba@omu.ac.jp., Gupta RK; Protein Biochemistry Research Centre, Dr D. Y. Patil Biotechnology and Bioinformatics Institute, Dr D. Y. Patil Vidyapeeth, Tathawade, Pune 411033, Maharashtra, India. rajeshkumar.gupta@dpu.edu.in. |
| Jazyk: |
angličtina |
| Zdroj: |
Biomaterials science [Biomater Sci] 2024 Mar 12; Vol. 12 (6), pp. 1490-1501. Date of Electronic Publication: 2024 Mar 12. |
| DOI: |
10.1039/d3bm01746j |
| Abstrakt: |
Cross-presentation, exogenous antigen presentation onto major histocompatibility complex class I molecules on antigen presenting cells, is crucially important for inducing antigen-specific cellular immune responses for cancer immunotherapy and for the treatment of infectious diseases. One strategy to induce cross-presentation is cytosolic delivery of an exogenous antigen using fusogenic or endosomolytic molecule-introduced nanocarriers. Earlier, we reported liposomes modified with pH-responsive polymers to achieve cytosolic delivery of an antigen. Polyglycidol-based or polysaccharide-based pH-responsive polymers can provide liposomes with delivery performance of antigenic proteins into cytosol via membrane fusion with endosomes responding to acidic pH, leading to induction of cross-presentation. Mannose residue was introduced to pH-responsive polysaccharides to increase uptake selectivity to antigen presenting cells and to improve cross-presentation efficiency. However, direct introduction of mannose residue into pH-responsive polysaccharides suppressed cytoplasmic delivery performance of liposomes. To avoid such interference, for this study, mannose-containing glycans were incorporated separately into pH-responsive polysaccharide-modified liposomes. Soybean agglutinin-derived glycopeptide was used as a ligand for lectins on antigen presenting cells. Incorporation of glycopeptide significantly increased the cellular uptake of liposomes by dendritic cell lines and increased cross-presentation efficiency. Liposomes incorporated both glycopeptide and pH-responsive polysaccharides exhibited strong adjuvant effects in vitro and induced the increase of dendritic cells, M1 macrophages, and effector T cells in the spleen. Subcutaneous administration of these liposomes induced antigen-specific cellular immunity, resulting in strong therapeutic effects in tumor-bearing mice. These results suggest that separate incorporation of glycopeptides and pH-responsive polysaccharides into antigen-loaded liposomes is an effective strategy to produce liposome-based nanovaccines to achieve antigen cross-presentation and induction of cellular immunity towards cancer immunotherapy. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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