Manganese has recently been exploited for
cancer immunotherapy, fenton-like reaction-mediated chemo-dynamic
therapy, and magnetic resonance imaging. The integration of multiple roles of
manganese into one platform is of great significance for
cancer theranostics and
tumor inhibition. Here, we designed a multifunctional nanoplatform based on
manganese, which consisted of a
manganese-containing inner core and a
phospholipid bilayer shell co-loaded with
glucose oxidase (GOx),
paclitaxel (PTX), and a NIR
fluorescent dye (NanoMn-GOx-PTX). In a pH-dependent manner, the nanoplatform released
manganese ions and payloads inside the
tumor cells. In vitro characterization and cellular experiments indicated that NanoMn-GOx-PTX could catalyze the conversion of
glucose into
reactive oxygen species (ROS) through a cascade Fenton-like reaction as well as release free PTX. The consumption of
glucose, ROS production, and the chemotherapeutic effect of PTX contributed to the superior cytotoxicity and apoptosis of 4T1
cancer cells. Moreover, NanoMn-GOx-PTX effectively induced the production of large amounts of
type I interferon and pro-inflammatory
cytokines in vivo, activating the innate immune response. Through the synergistic functions of the above components, NanoMn-GOx-PTX exerted the strongest anti-
tumor effect in 4T1
tumor-bearing models. Therefore, the
manganese-based nanoplatform could serve as a promising
theranostic tool for
breast cancer therapy. STATEMENT OF SIGNIFICANCE: 1) This nanoplatform can be used as a universal tool for delivering
proteins and anticancer drugs into cells; 2) The PEG-modified
phospholipid bilayer shell plays a significant role in retarding the release of overloaded
manganese ions and drugs in a pH-sensitive manner; 3) The released Mn2+ has the ability to enhance T1 contrast in magnetic resonance imaging; 4) The released Mn2+ can function as nanoadjuvants to activate the cGAS-
STING pathway and effectively induce the natural immune response;5) The overloaded
manganese ions are combined with
glucose oxidase to form a cascade reaction system, indirectly converting
glucose into ROS to induce oxidative damage of
tumor tissue.