Osteoporosis
(OP) is one of the most common diseases in the elderly,
and it is not effectively solved by current treatments. Mesenchymal
stem cells (MSCs) have multiple differentiation potentials, which
can induce osteogenic differentiation to treat OP; however, it is
important to understand how to remotely control and detect osteogenic
differentiation in vivo in real time. Here, we developed
an upconversion nanoparticle (UCNP)-based photoresponsive nanoplatform
for near-infrared (NIR) light-mediated control of intracellular icariin
(ICA) release to regulate the osteogenic differentiation of MSCs for
OP therapy. We simultaneously detected osteogenic differentiation in vivo in real time to evaluate the treatment effects.
The Tm/Er-doped UCNPs were synthesized and coated with mesoporous
silica (UCNP@mSiO2) first. Then, the photocaged linker
4-(hydroxymethyl)-3-nitrobenzoic acid (ONA) and the PEG linker (OH-PEG4-MAL)
were linked to the surface of UCNP@mSiO2 to conjugate to
the cap β-cyclodextrin (β-CD) and the Arg-Gly-Asp (RGD)-targeted
peptide/matrix metalloproteinase 13 (MMP13)-sensitive peptide-BHQ
(CGPLGVRGK-BHQ3) to form the UCNP nanoplatform (UCNP@mSiO2-peptide-BHQ-ONA-CD) for drug loading. Under 980 nm NIR light,
the upconverted UV from the UCNPs triggered the cleavage of cap β-CD
and the intracellular release of ICA to induce the osteogenic differentiation
of MSCs for OP therapy. Meanwhile, MMP13, which was produced by osteogenic
differentiation of MSCs, cleaved the MMP13-sensitive peptide to remove
BHQ and recover the fluorescence of UCNPs, allowing real-time detection
of osteogenic differentiation and the evaluation of the OP treatment
effect. This photoresponsive UCNP nanoplatform has the potential to
be used for the remote control and real-time detection of osteogenic
differentiation of MSCs for OP therapy by NIR.