NIR-Triggered Release of Nitric Oxide by Upconversion-Based Nanoplatforms to Enhance Osteogenic Differentiation of Mesenchymal Stem Cells for Osteoporosis Therapy

Author:

Ma Xulu1,Luan Zhao1,Zhao Qingxin1,Yang Anli2,Li Jinming1ORCID

Affiliation:

1. MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, Guangdong Provincial Key Laboratory of Laser Life Science, Guangzhou Key Laboratory of Spectral Analysis and Functional Probes, College of Biophotonics, South China Normal University, Guangzhou 510631, China.

2. Department of Breast Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou 510060, China.

Abstract

Stem cell therapy is an attractive approach to bone tissue regeneration in osteoporosis (OP); however, poor cell engraftment and survival within injured tissues limits its success in clinical settings. Nitric oxide (NO) is an important signaling molecule involved in various physiological processes, with emerging evidence supporting its diverse roles in modulating stem cell behavior, including survival, migration, and osteogenic differentiation. To control and enhance osteogenic differentiation of mesenchymal stem cells (MSCs) for OP therapy, we designed a near-infrared (NIR) light-triggered NO-releasing nanoplatform based on upconversion nanoparticles (UCNPs) that converts 808-nm NIR light into visible light, stimulating NO release by light control. We demonstrate that the UCNP nanoplatforms can encapsulate a light-sensitive NO precursor, Roussin’s black salt (RBS), through the implementation of a surface mesoporous silica coating. Upon exposure to 808-nm irradiation, NO is triggered by the controlled upconversion of UCNP visible light at the desired time and location. This controlled release mechanism facilitates photoregulated differentiation of MSCs toward osteogenic lineage and avoids thermal effects and phototoxicity on cells, thus offering potential therapeutic applications for treating OP in vivo. Following the induction of osteogenic differentiation, the UCNP nanoplatforms exhibit the capability to serve as nanoprobes for the real-time detection of differentiation through enzymatic digestion and fluorescence recovery of UCNPs, enabling assessment of the therapeutic efficacy of OP treatment. Consequently, these UCNP-based nanoplatforms present a novel approach to control and enhance osteogenic differentiation of MSCs for OP therapy, simultaneously detecting osteogenic differentiation for evaluating treatment effectiveness.

Funder

National Natural Science Foundation of China

Publisher

American Association for the Advancement of Science (AAAS)

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