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One arrow two eagles: Multifunctional nano-system for macrophage reprogramming and osteoclastogenesis inhibition
Tong Sha1,2, Ze Wang3, Jinwei Li1,2
1Department of Oral Pathology, Hospital of Stomatology, Jilin University, Changchun, 130021, PR China.
Abstract:
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.
Insights
A novel nano-system, AuNDs-sCT, effectively treats inflammatory osteolysis by inhibiting osteoclast formation and reversing inflammation. This dual-action approach offers a synergistic therapeutic strategy for bone health.
Area of Science:
- Biomaterials Science
- Immunology
- Nanotechnology
Background:
- Inflammatory osteolysis is a significant global health concern.
- Current monotherapies for inflammatory osteolysis have limited efficacy due to the complex bone immune system.
- Targeting both osteoclast formation and the inflammatory microenvironment is crucial for effective treatment.
Purpose of the Study:
- To design a multifunctional nano-system (AuNDs-sCT) for synergistic treatment of inflammatory osteolysis.
- To inhibit osteoclast (OC) differentiation and reverse the inflammatory microenvironment.
- To evaluate the therapeutic efficacy and potential as a fluorescent probe.
Main Methods:
- Modification of salmon calcitonin (sCT) to create AuNDs-sCT nano-system.
- Assessment of AuNDs-sCT's effect on OC differentiation via calcitonin receptor binding.
- Evaluation of anti-inflammatory and antioxidant effects, including macrophage polarization (M1 to M2) via NF-κB pathway inhibition.
- Utilizing AuNDs-sCT as a fluorescent probe for real-time visualization.
Main Results:
- AuNDs-sCT effectively restrained OC differentiation and down-regulated OC-specific genes/proteins.
- The nano-system reversed the inflammatory microenvironment by promoting M2 macrophage polarization.
- AuNDs-sCT demonstrated antioxidant and anti-inflammatory properties.
- The system functioned as a fluorescent probe for monitoring treatment.
Conclusions:
- AuNDs-sCT offers a synergistic "one arrow two eagles" therapeutic strategy for inflammatory osteolysis.
- The nano-system inhibits OC differentiation and reprograms macrophages, providing an effective treatment option.
- Drug repurposing and advanced nanotechnology offer new avenues for managing inflammatory bone diseases.
