Bioactive silica nanoparticles target autophagy, NF-κB, and MAPK pathways to inhibit osteoclastogenesis.

Spherical 50 nm silica-based nanoparticles (SiNPs) promote healthy bone homeostasis and maintenance by supporting bone forming osteoblast lineage cells while simultaneously inhibiting the differentiation of bone resorbing osteoclasts. Previous work demonstrated that an intraperitoneal injection of SiNPs in healthy mice - both young and old - increased bone density and quality, suggesting the possibility that SiNPs represent a dual action therapeutic. However, the underlying mechanisms governing the osteoclast response to SiNPs have yet to be fully explored and defined. Therefore, the goals of this study were to investigate the cellular and molecular mechanisms by which SiNPs inhibit osteoclastogenesis. SiNPs strongly inhibited RANKL-induced osteoclast differentiation within the first hours and concomitantly inhibited early transcriptional regulators such as Nfatc1. SiNPs simultaneously stimulated expression of autophagy related genes p62 and LC3ß dependent on ERK1/2 signaling pathway. Intriguingly, SiNPs were found to stimulate autophagosome formation while inhibiting the autophagic flux necessary for RANKL-stimulated osteoclast differentiation, resulting in the inhibition of both the canonical and non-canonical NF-κB signaling pathways and stabilizing TRAF3. These results suggest a model in which SiNPs inhibit osteoclastogenesis by inhibiting the autophagic machinery and RANKL-dependent functionality. This mechanism of action defines a novel therapeutic strategy for inhibiting osteoclastogenesis.

Zoledronate and SPIO dual-targeting nanoparticles loaded with ICG for photothermal therapy of breast cancer tibial metastasis.

Currently, nanoparticles (NPs) for cancer photothermal therapy (PTT) have limited in vivo clearance, lack targeting ability and have unsatisfactory therapeutic efficiency. Herein, we report a dual-targeting and photothermally triggered nanotherapeutic system based on superparamagnetic iron oxide (Fe3O4) and indocyanine green (ICG)-entrapped poly-lactide-co-glycolide modified by ZOL (PLGA-ZOL) NPs (ICG/Fe3O4@PLGA-ZOL) for PTT of breast cancer tibial metastasis, which occurs frequently in the clinic and causes challenging complications in breast cancer. In this system, both ICG and Fe3O4 can convert light into heat, while NPs with Fe3O4 and ZOL can be attracted to a specific location in bone under an external magnetic field. Specifically, the dual-targeting and double photothermal agents guaranteed high accumulation in the tibia and perfect PTT efficiency. Furthermore, the in vivo studies showed that ICG/Fe3O4@PLGA-ZOL NPs have extraordinary antitumor therapeutic effects and that these NPs can be accurately located in the medullary cavity of the tibia to solve problems with deep lesions, such as breast cancer tibial metastasis, showing great potential for cancer theranostics.

Near-infrared-induced IR780-loaded PLGA nanoparticles for photothermal therapy to treat breast cancer metastasis in bones.

Nanodrug-based cancer therapy, especially when treating bone metastases, faces the problem of limited therapeutic efficacy. In this work, we reported a photothermally triggered nanomaterial based on IR780-entrapped poly-lactide-co-glycolide (PLGA) nanoparticles (IR780@PLGA NPs) for the photothermal therapy of bone metastases of breast cancer, in which IR780 converted light into heat to play a role in "burning" the tumors. Anti-tumor therapy studies showed the impressive effectiveness of IR780@PLGA NPs in the photothermal therapy (PTT) of bone metastases. As a result, the IR780@PLGA NPs show a great potential for controlling the bone metastases of breast cancer.

S100A8/A9 in Inflammation.

S100A8 and S100A9 (also known as MRP8 and MRP14, respectively) are Ca2+ binding proteins belonging to the S100 family. They often exist in the form of heterodimer, while homodimer exists very little because of the stability. S100A8/A9 is constitutively expressed in neutrophils and monocytes as a Ca2+ sensor, participating in cytoskeleton rearrangement and arachidonic acid metabolism. During inflammation, S100A8/A9 is released actively and exerts a critical role in modulating the inflammatory response by stimulating leukocyte recruitment and inducing cytokine secretion. S100A8/A9 serves as a candidate biomarker for diagnosis and follow-up as well as a predictive indicator of therapeutic responses to inflammation-associated diseases. As blockade of S100A8/A9 activity using small-molecule inhibitors or antibodies improves pathological conditions in murine models, the heterodimer has potential as a therapeutic target. In this review, we provide a comprehensive and detailed overview of the distribution and biological functions of S100A8/A9 and highlight its application as a diagnostic and therapeutic target in inflammation-associated diseases.