Mannose-functionalized thermoresponsive microneedles for enhanced antigen delivery and immune activation.

Authors

Siyang Liu, Yong Pan, Miao Pang, Lu Shi, Yanxin Qi, Haihua Xiao, Yubin Huang

Published in

Journal of materials chemistry. B. Aug 27, 2026. Epub Aug 27, 2026.

Abstract

Stimuli-responsive microneedles (MNs) constitute a promising vaccine delivery platform through spatiotemporally programmed antigen release, enabling innate immunity-synchronized delivery, microenvironment-tunable immunogenicity, and controlled lymphoid targeting for enhanced vaccine potency. Herein, we developed thermoresponsive MNs using a hybrid matrix (HNM) of mannose-functionalized poly(N-isopropylacrylamide) (PNIPAM) and hyaluronic acid (HA) for controlled antigen delivery and immune activation. The MNs were fabricated via a template-based method, with mannose-conjugated PNIPAM enabling temperature-triggered release above its lower critical solution temperature (LCST) and accelerated release at physiological temperature, while HA enhances mechanical integrity (failure force: 0.77 N needle^-1) and biodegradability. In vitro and in vivo release studies demonstrated temperature-dependent ovalbumin (OVA) release (2.14 µg/14 min at 37 °C; 67.3% within 24 h in vivo) and prolonged retention (72 h). Intracellular co-localization confirmed mannose receptor-mediated uptake of the antigen-carrier complex. Flow cytometry revealed 84.0% dendritic cell recruitment and 67.6% splenic lymphocyte proliferation. Furthermore, antigen-loaded HNM-MNs demonstrated superior therapeutic efficacy in both the B16-F10 melanoma model and influenza B hemagglutinin (Hem) viral challenge model. This work introduces a dual-functional platform integrating mannose-targeted delivery and thermoresponsive release, offering an effective strategy to improve subunit vaccine efficacy by enabling precise antigen release and enhanced immune activation.

PMID:
42657667
Bibliographic data and abstract were imported from PubMed on 27 Aug 2026.

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