Immunotherapeutic efficacy of transdermal delivery of anti-CD3 antibody-conjugated magnetic nanoparticles using a hyaluronic acid-based dissolving microneedle patch.

Transdermal delivery of biologics remains challenging due to the stratum corneum barrier, which limits the clinical translation of antibody-based immunotherapies. In this proof-of-concept study, we developed a biodegradable hyaluronic acid (HA)-based dissolving microneedle (MN) patch incorporating anti-CD3 monoclonal antibody-conjugated magnetic nanoparticles (Ab-MNPs) as a minimally invasive transdermal immunomodulatory platform. Anti-CD3 antibodies were covalently conjugated to dextran-coated, amine-functionalized Fe₃O₄ nanoparticles using glutaraldehyde chemistry and subsequently incorporated into HA microneedles by mold replication. The fabricated MN arrays exhibited uniform morphology with well-defined needle structures and retained the magnetic responsiveness of the incorporated nanoparticles after fabrication. Therapeutic feasibility was evaluated in a concanavalin A (ConA)-induced inflammatory mouse model. Animals received one, two, or three identical MN patches before ConA challenge, followed by measurement of serum interleukin-6 (IL-6) and interferon-gamma (IFN-γ). Compared with the untreated inflammatory control, MN-treated groups showed reduced circulating IL-6 and IFN-γ concentrations, with a general patch-number-associated trend toward greater cytokine reduction. Because antibody loading, delivered dose, pharmacokinetics, biodistribution, and local release kinetics were not quantified, these findings should be interpreted as preliminary evidence of biological activity rather than confirmation of a quantitative dose-response relationship or CD3-specific immunomodulatory mechanism. Overall, this study demonstrates the feasibility of integrating antibody-conjugated magnetic nanoparticles into a biodegradable HA microneedle platform for minimally invasive transdermal delivery and provides a foundation for future investigations incorporating quantitative drug delivery analysis, mechanistic immunological evaluation, pharmacokinetic characterization, biodistribution studies, and comprehensive safety assessment to facilitate translational development.