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.
Cell adhesion and differentiation can be regulated through material engineering, but current methods have low temporal and spatial accuracy to control in vivo. Here, we developed an up-conversion nanoparticle (UCNP) substrate to regulate cell adhesion and multidifferentiation in mesenchymal stem cells (MSCs) by near-infrared (NIR) light. First, the celladhesive peptide Arg-Gly-Asp (RGD) was conjugated on the surface of UCNPs, and the photocleavage 4-(hydroxymethyl)-3nitrobenzoic acid (ONA) was connected to RGD. Then, the photoactivated UCNPs were linked to cover glass to form UCNPsubstrate. Under the NIR, the up-convert UV from UCNPs triggered the release of ONA and exposed RGD to change the cellmatrix interactions dynamically for cell adhesion and spreading. Moreover, MSCs cultured on UCNP-substrate could be specifically induced to multidifferentiate adipocytes or osteoblasts via different power and periods of NIR irradiation in vitro and in vivo. Our work demonstrates a new way to control cell adhesion and multidifferentiation by light for regeneration medicine.
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