Mesenchymal stem cell (MSC) therapy has been proven to
be a potentially
effective approach for idiopathic pulmonary fibrosis (IPF) treatment.
However, this strategy is currently limited by the poor curative effect
and an insufficient comprehension of the in vivo condition
of the transplanted MSCs in the remedy of IPF. To address these issues,
herein, a nanosystem composed of Janus Au/mesoporous silica core/shell
nanoparticles (Janus NPs) is designed for effective therapeutic and
real-time tracing of MSCs in MSC-based IPF therapy. The Janus NPs
consist of a Au core and a pirfenidone (PFD)-loaded mesoporous silica
shell asymmetrically decorated with two targeting moieties: one is
reactive oxygen species (ROS)-sensitive thioketal grafted methoxy
poly(ethylene glycol) (mPEG-TK), and the other is 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE). The asymmetric
decoration on each side of the particle allows long-term anchoring
of the Janus NPs on the cell membrane to facilitate the responsive
release of PFD in the ROS environment of the fibrotic lung, thereby
enhancing the therapeutic efficacy of the transplanted MSCs by improving
the microenvironment. Following drug release, the Janus NPs quickly
enter into MSCs, achieving long-term computed tomography (CT) imaging
tracing of MSCs in IPF model mice for an in-depth comprehension of
the cell therapy mechanism. Overall, this work reports on Janus Au/PFD-loaded
mesoporous silica core/shell NPs that combine the drug delivery and
imaging tracking of MSCs, which may provide a strategy for the stem
cell-based treatment of IPF.