Bone metastasis is a common metastasis site such as lung cancer, prostate cancer, and other malignant tumors. The occurrence of bone metastases of lung cancer is often accompanied by bone loss, fracture, and other skeletal-related events (SREs) caused by tumor proliferation and osteoclast activation. Furthermore, along with the differentiation and maturation of osteoclasts in the bone microenvironment, it will further promote the occurrence and development of bone metastasis. Protein drugs are one of the most promising therapeutic pharmaceuticals, but in vivo delivery of protein therapeutics still confronts great challenges. In order to more effectively conquer bone metastases and alleviate SREs, herein, we constructed biomineralized metal–organic framework (MOF) nanoparticles carrying protein toxins with both bone-seeking and CD44-receptor-targeting abilities. More importantly, through combination with Receptor Activator of Nuclear Factor-κ B Ligand (RANKL) antibody, in vivo results demonstrated that these two protein agents not only enhanced the detraction effects of protein toxin agents as ribosome-inactivating protein (RIP) on bone metastatic tumor cells but also exhibited synergistic intervention of the crosstalk between bone cells and tumor cells and reduced SREs such as bone loss. Collectively, we expect that this strategy can provide an effective and safe option in regulating bone-tumor microenvironments to overcome bone metastasis and SREs.

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The progression of osteoarthritis is associated with chronic synovitis caused by synovial macrophage infiltration and proinflammatory M1 polarization. Accordingly, repolarization of macrophages from the M1 to M2 phenotype by nanoagents is proposed as a potential treatment strategy. However, achieving adequate effects using intra-articular injected agents is challenging due to the rapid drug clearance from the joint space and poor efficiency of nanoparticles endocytosis by synovial macrophage cells. Herein, apoptotic chondrocyte membrane-coated, quercetin-loaded metalorganic framework nanoparticles as immunomodulators for treating osteoarthritis are reported. The apoptotic chondrocyte membrane-camouflaged nanoparticles containing various natural "eat me" signals can be easily disguised as chondrocyte apoptotic bodies in the joints, and thus are more easily phagocytized by synovial macrophages similarly to efferocytosis. Furthermore, the released quercetin promotes the polarization of synovial macro phages to the M2 phenotype and also inhibites the apoptosis of articular chondrocytes. In vivo results suggest that such a "Trojan horse" strategy can extend the retention time of nanoparticles in osteoarthritis joints and improve treatment efficacy. Collectively, it is hoped that this study can offer a potential and universal platform for engineered cell membranecoated nanoparticles to resolve inflammation by simulating specific inflammatory processes.

Tumor bone metastasis is an important cause of tumor recurrence and death.

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