A metabolic amplification strategy for spherical nucleic acid immunogenicity driven by simvastatin-CpG codelivery.

Authors

Lulu Zhang, Lin Yu, Jiaxi Zhu, Yuan Ding, Zheng Wang, Ruihong Yu, Lina Jiao, Zhimin Zhang, Yan Ma, Jinli Shi, Zhenguang Liu

Published in

Materials today. Bio. Volume 39. Pages 103426. Epub Jun 30, 2026.

Abstract

Spherical nucleic acids (SNAs) are a promising platform for immunotherapy, although their limited innate immune activation may constrain therapeutic performance. Here, we report a simvastatin-CpG SNAs (S-SNAs) system that integrates a metabolic modulator with CpG to enhance immune activation. Mechanistically, simvastatin is found to potentiate CpG-induced innate immune signaling, likely through modulation of the mevalonate pathway, resulting in regulated macrophage activation in vitro. Integration into the SNAs architecture is associated with improved cellular uptake and enhanced RBD-specific humoral immune responses in vivo. In a murine melanoma model, the engineered S-SNAs exhibit antitumor activity and are associated with prolonged survival under the experimental conditions, without evident systemic toxicity. Overall, this work suggests that metabolic modulation may represent a useful strategy for improving the immunological performance of nucleic acid-based nanostructures.

PMID:
42434730
Bibliographic data and abstract were imported from PubMed on 11 Jul 2026.

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