Manganese is a transition metal that is an essential
trace element
for human health. Manganese ions (Mn
2+
), which serve as
one of the most common transition metal ions, play vital roles in
enhancing innate immune responses. However, immune agonists based
on Mn
2+
are poorly utilized in clinical trials due to poor
chemodynamics and adverse events. In this work, we designed a novel
delivery carrier for loading manganese ions by constructing hFn-MT3(Mn
2+
) protein nanoparticles (termed as NPs(Mn
2+
)),
which contained human ferritin heavy chain (hFn) and metallothionein-3
(MT3), induced by isopropyl β-
d
-thiogalactoside (IPTG)
and manganese ions in the prokaryotic expression system. The NPs(Mn
2+
) protein nanoparticles could not only stimulate immune cell
proliferation but also activate innate immune responses via the cGAS-STING-IRF3
signaling pathway. Collectively, our results unveil a candidate strategy
for delivering metal ions beyond Mn
2+
and may broaden metal
ion clinical use in the field of immunotherapies.