Prussian Blue Nanozyme Normalizes Microenvironment to Delay Osteoporosis

Abstract

Osteoporosis (OP) is the most common orthopedic disease in the elderly and the main cause of age‐related mortality and disability. However, no satisfactory intervention is currently available in clinical practice. Thus, an effective therapy to prevent or delay the development of OP should be devised. Osteoclastogenesis overactivation and excessive bone resorption are the main characteristics of OP. Accordingly, a paradigm for nanozyme‐mediated normalization of the disease microenvironment to regulate osteoclast differentiation and delay OP is proposed. Hollow Prussian blue nanozymes (HPBZs) are prepared via template‐free hydrothermal synthesis and selected as representative nanozymes. The intrinsic osteoclast activity‐remodeling bioactivities of the HPBZs are explored in vitro and in vivo, focusing on their impact on osteogenesis and specific molecular mechanisms using an OP murine model. The HPBZs significantly normalize the OP microenvironment, thereby inhibiting osteoclast formation and osteoclast resorption, possibly owing to the suppression of intracellular reactive oxygen species generation, the mitogen‐activated protein kinase, and nuclear factor κB signaling pathways. Consistently, in an ovariectomy‐induced OP murine model, HPBZ treatment significantly attenuates osteoporotic bone loss in vivo. The findings confirm the HPBZ‐mediated normalization of the disease microenvironment for the treatment of OP and suggest its application to other inflammation‐related diseases.

Progress in the preparation of Prussian blue-based nanomaterials for biomedical applications

“…They verified that the Bi-HMPBAs osteoclast formation and resorption can be inhibited by regulating oxidative stress, thereby effectively delaying the further development of OP. 16 High ROS levels, a characteristic pathological change in arthritis, increase hypoxia-inducible factor 1α (HIF 1α) levels and promote synovial inflammation. Fan et al used bovine serum albumin (BSA) bubble template to prepare Mn-HMPBAs with MnCl 2 and K 4 Fe(CN) 6 by co-precipitation method, which synergistically scavenged ROS and alleviated hypoxia to reduce inflammation.…”

“…This makes it have excellent multi-type enzyme activities, including the inhibition of tumor growths and metastasis, and achieving therapeutic effects. 16,17 Photothermal therapy is a new cancer treatment method that has emerged in recent years. 18 In general, the traditional photothermal nanomaterials are mainly gold nanoparticles, 19 silver nanoparticles, 20 carbon nanoparticles, 21 platinum nanoparticles 22 and their derivatives.…”

Myrislignan Targets Extracellular Signal-regulated Kinase (ERK) and Modulates Mitochondrial Function to Dampen Osteoclastogenesis and Ovariectomy-i nduced Osteoporosis

“…The induction of osteoclast differentiation is in connection with the binding of RANK to RANKL (7,10). And then, RANKL/RANK signaling gives rise to the collection of TNF receptor-associated factor 6 (TRAF6) (9), inducing the mobilization of several subsequent pathways, such as mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways (11,21), which are classical pathways related to osteoclast differentiation (10). NFATc1, the critical osteoclastogenesis-controlling master transcription factor, is subsequently initiated to express by RANKL (10).…”

“…Bone health is strictly regulated, while osteoporosis occurs mainly due to the disruption of bone homeostasis, which depends on the balance between osteoclastic bone resorption and osteoblastic bone formation (2,5). As the only specialized multinucleated cells derived from the mononuclear macrophage lineage in vivo (6), osteoclasts could be activated under the stimulation of various pathological factors (7) (chronic use of drugs, immobilization, malnutrition, and chronic in ammation) to accelerate bone resorption (8, 9), leading to osteoporosis and osteoporosis-related diseases, including Alzheimer's disease, diabetes and cancers and so on (10,11). Therefore, inhibiting the formation and activity of osteoclasts is a crucial strategy for treating osteoporosis.…”

Ca/Fe-Based Nanozymes Relieve Severe Acute Pancreatitis by Ferroptosis Regulation and Reactive Oxygen Species Scavenging

“…27,28 PB nanozymes with superoxide dismutase (SOD)-and peroxidase (POD)-simulated activity can convert excess harmful oxygen radicals into harmless products. 29 The biological applications of PB nanozymes are studied in many diseases, including osteoporosis, 30 radiation-induced hematopoietic injury, 31 experimental lung adenocarcinoma, and anthracycline-induced liver injury. 32 However, the mechanisms of nanozymes in the treatment of ROS-related SAP remain unclear; it is of significance to develop novel nanozymes and deeply understand the therapeutic mechanism for the achievement of therapeutic applications.…”