Breast
cancer metastases to bone poses a significant challenge
for the administration of treatment strategies. The bone microenvironment,
metastatic tumor cells, osteoclasts, and tumor-associated macrophages
(TAMs) all play crucial and synergistic roles in creating a favorable
environment for the proliferation, progression, and survival of the
metastatic tumor, which in turn induces osteoclast-mediated bone destruction.
In this study, we functionalized immunostimulatory cytosine–phosphate–guanosine
(CpG)-loaded metal–organic framework (MOF) nanoparticles with
bone targeting capabilities by surface modification with FDA approved
antiresorptive bisphosphonate, zoledronic acid (ZOL). The functionalized
bone targeting immunostimulatory MOF (BT-isMOF) nanoparticles demonstrates
strong binding to calcium phosphate in vitro and exhibits specific
targeting and accumulation in bone tissues in vivo. In vitro cellular
and biochemical analyses demonstrated that the BT-isMOF nanoparticles
could potently inhibit osteoclast formation and concomitantly induce
macrophages polarization toward the M1 pro-inflammatory phenotype.
Finally, using the intratibial murine model of breast cancer bone
metastasis, we showed that the administration of BT-isMOF nanoparticles
significantly suppressed osteoclast-mediated bone destruction and
enhanced polarization of tumor-resident macrophages to M1 phenotype.
Together, our data provides promising evidence for the potential therapeutic
application of the BT-isMOF nanoparticles in the treatment of breast
cancer bone metastases.
Discography often destroys the hypoxic environment in the intervertebral disc and accelerates intervertebral disc degeneration (IVDD). Therefore, it often fails to meet the requirements for application in clinical practice. This technology mainly increases the reactive oxygen species (ROS) in the IVD. As so, it is particularly critical to develop strategies to avoid this degeneration mechanism. Prussian blue nanoparticles (PBNPs) are found to enhance development under magnetic resonance T1 and have antioxidant enzyme activity. The key results of the present study confirm that PBNPs alleviate intracellular oxidative stress and increase the intracellular activities of antioxidant enzymes, such as superoxide dismutase 1 (SOD1). PBNPs can rescue nucleus pulposus cell degeneration by increasing oxidoreductase system-related mRNA and proteins, especially by stabilizing SOD1 from ubiquitination-proteasome degradation, thus improving the mitochondrial structure to increase antioxidation ability, and finally rescuing ROS-induced IVDD in a rat model. Therefore, it is considered that PBNPs can be a potential antioxidation-protective discography contrast agent.
Osteoclasts are the main cells of normal bone remodeling and pathological bone destruction in vivo. Overactivation of osteoclasts can lead to osteolytic diseases including breast cancer bone tumors, arthritis, aseptic...
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