Chiral‐Selective Antigen‐Presentation by Supramolecular Chiral Polymer Micelles

Abstract

Chirality is ubiquitous in biological systems, which is closely related to biological functions, life processes, and even the pathogenesis of diseases. However, the interface between the chirality of synthetic materials and organisms, particularly the immune system, remains poorly understood. Here, supramolecular chiral polymer micelles (SCPMs) are prepared by complexing antigenic proteins with chiral amino acid‐modified polyethyleneimine. The introduction of chirality not only reduces the toxicity of cationic polymer, but also benefits cell uptake and antigen presentation. Especially, D‐chirality presents the lowest cytotoxicity, while promoting the highest expression level of costimulatory molecules on dendritic cells compared to L‐chirality and achirality. The superiority of D‐chirality to stimulate dendritic cell maturation is supported by immunization with D‐SCPMs, which achieves significant antigen‐specific proliferation of T cells in the spleen, lymph nodes, and tumor of mice. Chirality‐mediated antigen processing and presentation are demonstrated by D‐SCPMs self‐assembled from chiral alkaline histidine or neutral phenylalanine modified polyethyleneimine and tumor associated ovalbumin or severe acute respiratory syndrome coronavirus 2 spike 1 antigenic protein. Immunoactivation enabled by D‐chirality opens a window to prepare potent nanotherapeutics for disease prevention and treatment.

Harnessing Nanovaccines for Effective Immunization─A Special Concern on COVID-19: Facts, Fidelity, and Future Prospective

“…204 Micelles are a type of nanoparticle that presents antigens and self-assemble into a spherical shape, consisting of block copolymers with amphiphilic segments. 211 In the context of antigen presentation, micelles can serve as antigen carriers that enhance the strength and immunogenicity of the encapsulated antigens. By wrapping antigens within the water-hating core, micelles protect them from degradation, enzymatic activity, and immune recognition, prolonging their presence and enhancing their availability to antigen-presenting cells (APCs).…”

“…Micelles are a type of nanoparticle that presents antigens and self-assemble into a spherical shape, consisting of block copolymers with amphiphilic segments . In the context of antigen presentation, micelles can serve as antigen carriers that enhance the strength and immunogenicity of the encapsulated antigens.…”

Chiral amino acid modified boron-dipyrromethene nanoparticles with different photodynamic activities

“…[16][17][18][19][20][21][22] Chirality is one of the most important phenomena in nature and plays an important role in the living system. 23,24 However, chiral molecules function in various life processes only in a particular configuration. 25 For example, nucleotides and sugars in biological bodies are D-configurational, while phospholipids and amino acids are L-configurational.…”

Enantiomer-Dependent Supramolecular Immunosuppressive Modulation for Tissue Reconstruction

“…Sun et al discovered that d -cysteine-modified surfaces exhibited a weaker capacity in recruiting immune cells and immune activation compared to those coated with l -cysteine . Liu et al demonstrated that the immunoactivation effect of d -histidine-modified polyethylenimine is significantly enhanced compared to its corresponding L-chiral counterpart . Gao’s team and Wei’s team reported materials containing D-amino acids for immune regulation that convert macrophages from pro-inflammatory M1 to anti-inflammatory M2 phenotype. , In general, the utilization of multicomponent materials results in divergent conclusions and even contradictory results.…”