Supramolecular assembly of cholesterol-conjugated mannan and polyethylenimine into polyplex micelle: a potential biocompatible vaccine adjuvant platform

초록

The development of potent subunit vaccines requires adjuvant systems capable of eliciting robust cellular (Th1) immunity while maintaining high biocompatibility. Herein, we engineered a novel 'safety-by-design' nanoadjuvant platform via the supramolecular co-assembly of cholesteryl-conjugated mannan (MN-CLS) and cholesteryl-conjugated branched polyethylenimine (BPEI-CLS). This design induced the spontaneous formation of polyplex micelles driven by a 'dual-lock' mechanism: electrostatic attraction between the cationic BPEI and anionic mannan, reinforced by hydrophobic associations between cholesterol domains. Structural characterization (1H-NMR) confirmed successful synthesis, and the resulting micelles exhibited superior thermodynamic stability with a significantly reduced critical micelle concentration. fluorescence resonance energy transfer and dynamic light scattering analyses verified a unified core-shell architecture of approximately 200 nm, which is suitable for antigen-presenting cell-mediated cellular uptake and subsequent lymph node delivery. Crucially, in vitro assays demonstrated that MN-CLS/CLS-BPEI micelles significantly reduced cytotoxicity compared to native BPEI and BPEI-CLS while maintaining colloidal stability. This platform is expected to effectively synergizes the receptor-targeting specificity of mannan with the immunostimulatory potential of BPEI, presenting a promising, biocompatible adjuvant system for next-generation vaccines.

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