Mucin 1 Antigen Mimetic Functionalized Mannosylated Peptide Nanofibers for Antigen Uptake and Immune Modulation

14 May 2025, Version 1

Abstract

In this work, immune modulation of the monocyte-derived dendritic cells was studied by in vitro cell culture and organ-on-chip models. Self-assembled mannosylated peptide nanofibers were prepared and integrated with the MUC1 TnThr mimetic Tn-MIM to stimulate DCs’ maturation and differentiation. Man-PA/Tn-MIM nanofibers displayed remarkable cell-penetrating capabilities, also allowing the correct presentation of the antigen mimetic with a corresponding induction of lymphocytes, iNKT and NK cells recruitment. The Tn-MIM integrated nanofibrers were also found to direct immune response towards Th1 phenotype which is responsible for the production of cellular and humoral immunity. Organ-on-chip tests confirmed the cytotoxicity of lymphocytes stimulated with DC exposed to Man-PA/Tn-MIM. These results will help in the development of immunotherapies avoiding complications due to heterogeneous antigen display and to the use of adjuvants.

Keywords

Glycopeptides
TACA
Tn antigen
glycomimetic
immunostimulation

Supplementary materials

Title
Description
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Title
Methods and materials, supplementary figures and spectra
Description
Synthesis details, NMR spectra, CD spectra, TEM images of glyco-Pas, TEM images of florescent Tn-MIM integration, zeta potentials of glyco-PAs, cytockines evaluations, T cell activation and polarization assay, organ-on-chip model tests.
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