Near-Infrared Light-Controlled and Real-Time Detection of Osteogenic Differentiation in Mesenchymal Stem Cells by Upconversion Nanoparticles for Osteoporosis Therapy

Abstract

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.

Nanomedicine‐boosting icaritin-based immunotherapy of advanced hepatocellular carcinoma

“…Moreover, icaritin-based nanomedicines can be designed to release icaritin under certain conditions. Notably, a near infrared (NIR) light-responsive nanocarrier was designed for the controlled release of icariin [ 56 ]. In this study, icariin was loaded into mesoporous silica, and the formed nanomedicines were further covered with β-cyclodextrin (β-CD) through the linker 4-(hydroxymethyl)-3-nitrobenzoic acid (ONA).…”

One Stone Two Birds: An Upconversion Nanosensor for Sensitive Detection of Fluoroquinolones in Aquatic Products Based on Chelation Recognition

“…Similarly, carboxyl groups (COO−) in oleic acid also displayed symmetric and asymmetric stretching as vibrational peaks at 1560 and 1448 cm −1 , respectively (red line). 29,30 These peaks indicate the presence of oleic acid groups on the surface of UCNPs prior to silica shell modification. The absorption peaks associated with oleic acid were reduced or disappeared after coating the SiO 2 and modifying the amino group.…”

Near‐Infrared‐Responsive Rare Earth Nanoparticles for Optical Imaging and Wireless Phototherapy

“…[207] The UV-vis emission from UCL under NIR excitation stimulates the sequential photoisomerization of azo, which acts as an impeller pump that triggers the cyclic hybridization and dehybridization of DNA. In addition to the above systems, light-responsive drug release strategies based on UCNPs have been successfully employed for the photosensitive molecule 4-(hydroxymethyl)−3-nitrobenzoic acid, [208,209] a Ru-complex-based enzyme inhibition system, [210] the chemother- [206] Copyright 2016, Wiley-VCH. b) Schematic illustration of constructing UCL-driven DNA-azo nanopump and NIR-responsive drug release in living cells.…”