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Combination therapy based on sonodynamic therapy (SDT) combined with immune checkpoint blockers anti-PD-L1 provides effective anti-tumor effects. We designed a combination therapy based on M1/PLGA@IR780/CAT NPs of SDT-enhanced immunity combined with immune checkpoint blockers against PD-L1, which was based on M1 macrophage membrane-encapsulated poly (lactic-co-glycolic acid) (PLGA) nanoparticles loaded with the acoustic sensitizer IR780 and catalase (CAT) to successfully realize it. SDT based on M1/PLGA@IR780/CAT NPs could induce tumor cell death by promoting dendritic cell (DC) maturation and modulating the tumor immune microenvironment. In particular, the systemic anti-tumor immune response and potent immune memory induced upon combination with anti-PD-L1 checkpoint blockade not only alleviated the progression of mammary cancer in 4T1 mice and effectively blocked distant metastasis, but also prevented tumor recurrence, providing a promising new therapeutic strategy for clinical tumor therapy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Niu chengcheng reports financial support was provided by Niu, Chengcheng., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The wear particle-induced dissolution of bone around implants is a significant pathological factor in aseptic loosening, and controlling prosthetic aseptic loosening holds crucial social significance. While human umbilical cord mesenchymal stem cell-derived exosomes (HucMSCs-Exos, Exos) have been found to effectively promote osteogenesis and angiogenesis, their role in periprosthetic osteolysis remains unexplored. To enhance their in vivo application, we engineered HucMSCs-Exos-encapsulated poly lactic-co-glycolic acid (PLGA) nanoparticles (PLGA-Exos). In our study, we demonstrate that PLGA-Exos stimulate osteogenic differentiation while inhibiting the generation of reactive oxygen species (ROS) and subsequent osteoclast differentiation in vitro. In vivo imaging revealed that PLGA-Exos released exosomes slowly and maintained a therapeutic concentration. Our in vivo experiments demonstrated that PLGA-Exos effectively suppressed osteolysis induced by polyethylene particles. These findings suggest that PLGA-Exos hold potential as a therapeutic approach for the prevention and treatment of periprosthetic osteolysis. Furthermore, they provide novel insights for the clinical management of osteolysis., (© 2023. The Author(s).)

Bone metastasis (BM) is a solid tumor confined to narrow bone marrow cavities with a relatively poor blood supply and hypoxic environment, making conventional anticancer treatments difficult. In our study, we fabricated nanoparticles (NPs) based on zeolitic imidazolate framework-8 (ZIF-8) loaded with indocyanine green (ICG, a photodynamic agent) and cytochrome c (Cyt c, an anticancer protein) with a surface modified by zoledronate (ZOL, a bone-targeting moiety) and a polyvinyl pyrrolidone (PVP) coating to increase their stability. The ICG/Cyt c@ZZF-8 NPs were expected to have synergistic antitumor therapy and bone protection efficiency. The in vitro and in vivo experiments showed the bone-targeted and pH-sensitive ability of ICG/Cyt c@ZZF-8 NPs, which could be engulfed by tumor cells and release the cargos. Upon 780 nm laser irradiation, ICG produces cytotoxic reactive oxygen species (ROS, 1 O 2 ) that directly kill tumor cells, and Cyt c with catalase-like activity can induce programmed cell death and decompose H 2 O 2 to O 2 , thus enhancing the PDT efficiency. The ZOL can further inhibit bone resorption. The ICG/Cyt c@ZZF-8 NPs showed improved antitumor and bone protection efficiency in a mouse model of BM. This study demonstrated a potential mode for the synergetic therapy of orthopedic diseases.

Breast cancer bone metastasis is a terminal-stage disease and is typically treated with radiotherapy and chemotherapy, which causes severe side effects and limited effectiveness. To improve this, Sonodynamic therapy may be a more safe and effective approach in the future. Bacterial outer membrane vesicles (OMV) have excellent immune-regulating properties, including modulating macrophage polarization, promoting DC cell maturation, and enhancing anti-tumor effects. Combining OMV with Sonodynamic therapy can result in synergetic anti-tumor effects. Therefore, we constructed multifunctional nanoparticles for treating breast cancer bone metastasis. We fused breast cancer cell membranes and bacterial outer membrane vesicles to form a hybrid membrane (HM) and then encapsulated IR780-loaded PLGA with HM to produce the nanoparticles, IR780@PLGA@HM, which had tumor targeting, immune regulating, and Sonodynamic abilities. Experiments showed that the IR780@PLGA@HM nanoparticles had good biocompatibility, effectively targeted to 4T1 tumors, promoted macrophage type I polarization and DC cells activation, strengthened anti-tumor inflammatory factors expression, and presented the ability to effectively kill tumors both in vitro and in vivo, which showed a promising therapeutic effect on breast cancer bone metastasis. Therefore, the nanoparticles we constructed provided a new strategy for effectively treating breast cancer bone metastasis. [ABSTRACT FROM AUTHOR]