One arrow two eagles: Multifunctional nano-system for macrophage reprogramming and osteoclastogenesis inhibition against inflammatory osteolysis

Autor: Tong Sha, Ze Wang, Jinwei Li, Yahong Wu, Jinbiao Qiang, Zhenming Yang, Yue Hu, Kaijuan Zheng, Shuyu Zhang, Haizhu Sun, Andrew K. Whittaker, Bai Yang, Hongchen Sun, Quan Lin, Ce Shi
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Materials Today Bio, Vol 29, Iss , Pp 101285- (2024)
Druh dokumentu: article
ISSN: 2590-0064
DOI: 10.1016/j.mtbio.2024.101285
Popis: Inflammatory osteolysis poses a significant worldwide threat to public health. However, current monotherapies, which target either the prevention of the inflammatory response or the attenuation of osteoclast (OC) formation, have limited efficacy due to the complexity of the bone immune system being overlooked. Herein, by means of modifying salmon calcitonin (sCT), a multifunctional nano-system (AuNDs-sCT) was designed to synergistically inhibit OC differentiation and reverse the inflammatory microenvironment against inflammatory osteolysis. On the one hand, AuNDs-sCT effectively restrained OC differentiation by binding to the calcitonin receptors on the surface of OC precursors, resulting in the down-regulation of OC-specific genes and proteins. The targeted capacity of AuNDs-sCT provided a more durable and precise therapeutic effect. On the other hand, AuNDs-sCT exhibited antioxidant and anti-inflammatory effects, which regulated the polarization “switch” from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype in macrophages by the inhibition of NF-κB p65 phosphorylation, thereby effectively reversed the local inflammatory microenvironment. Additionally, AuNDs-sCT served as a promising fluorescent probe, enabling real-time visualization of the therapeutic process. This capability is expected to optimize drug administration and evaluate therapeutic effects. In summary, by inhibiting OC differentiation and reprogramming macrophages, AuNDs-sCT successfully realized drug repurposing and achieved the “one arrow two eagles” therapeutic strategy, which offers a synergistic and effective treatment option for the clinical management of inflammatory osteolysis.
Databáze: Directory of Open Access Journals