Phenolic Hydroxyl-Containing Lipid Nanoparticles Enable Codelivery of HPV Peptide Antigens and Manganese Adjuvant for Cancer Immunotherapy.

Authors

Shuang Hou, Deling Zhou, Yi Zhang, Youming Li, Dang Fan, Yeqin Hu, Liyan Li, Changjiang Qin, Mingxue Li, Ming Li, Hong Liu, Yongming Chen

Published in

ACS applied bio materials. Oct 28, 2026. Epub Oct 28, 2026.

Abstract

Therapeutic peptide vaccines against HPV-associated cancers are often limited by insufficient immunogenicity and inefficient intracellular delivery. Here, we develop a phenolic hydroxyl-containing lipid nanoparticle (EMT@LNP) as a nanomedicine platform for the coordinated codelivery of HPV16 E6/E7 peptide antigens and manganese (Mn2+) adjuvant. Distinct from conventional electrostatic loading strategies, EMT@LNP exploits hydrogen-bonding interactions between phenolic hydroxyl groups and peptide antigens, enabling charge-independent loading of peptides with diverse physicochemical properties, while coordination interactions between phenolic moieties and Mn2+ allow the simultaneous incorporation of immunostimulatory adjuvants. This dual-interaction-driven design integrates antigen delivery and innate immune activation within a single nanostructure. Functionally, EMT@LNP enhances antigen uptake and promotes dendritic cell maturation, accompanied by activation of STING-associated signaling, as indicated by increased phosphorylation of STING, TBK1, and IRF3. In vivo, EMT@LNP facilitates efficient delivery to draining lymph nodes and prolongs antigen retention following intramuscular administration. In a therapeutic TC-1 tumor model, EMT@LNP elicits potent antitumor immune responses, characterized by enhanced CD8+ T-cell infiltration and reduced immunosuppressive cell populations, leading to significant tumor growth inhibition without observable systemic toxicity. Collectively, this study presents a nanobiotechnology strategy that combines charge-independent peptide loading with metal-ion-mediated immune activation, providing a versatile and potentially translatable platform for therapeutic vaccination against HPV-associated malignancies.

PMID:
42947624
Bibliographic data and abstract were imported from PubMed on 28 Oct 2026.

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