Reversal of Osteoporotic Activity by Endothelial Cell-Secreted Bone Targeting and Biocompatible Exosomes.

Exosomes, also known as extracellular vesicles, are naturally occurring, biocompatible, and bioacive nanoparticles ranging from 40 to 150 nm in diameter. Bone-secreted exosomes play important roles in bone homeostasis, the interruption of which can lead to diseases such as osteoporosis, rheumatoid arthritis, and osteopetrosis. Though the relationship between vascular and bone homeostasis has been recognized recently, the role of vascular endothelial cell (EC)-secreted exosomes (EC-Exos) in bone homeostasis is not well understood. Herein, we found that EC-Exos show more efficient bone targeting than osteoblast-derived exosomes or bone marrow mesenchymal stem cell-derived exosomes. We also found that EC-Exos can be internalized by bone marrow-derived macrophages (BMMs) to alter their morphology. EC-Exos can inhibit osteoclast activity in vitro and inhibit osteoporosis in an ovariectomized mouse model. Sequencing of exosome miRNA revealed that miR-155 was highly expressed in EC-Exos-treated BMMs. The miR-155 level in EC-Exos was much higher than that in BMMs and ECs, indicating that miR-155 was endogenous cargo of EC-derived vesicles. Blockage of BMMs miR-155 levels reversed the suppression by EC-Exos of osteoclast induction, confirming that exosomal miR-155 may have therapeutic potential against osteoporosis. Taken together, our findings suggest that EC-Exos may be utilized as a bone targeting and nontoxic nanomedicine for the treatment of bone resorption disorders.

Biocompatible PEGylated Gold nanorods function As cytokinesis inhibitors to suppress angiogenesis.

Pathological angiogenesis is driven by uncontrolled growth of endothelial cells (ECs), which could lead to retinopathy, tumor and rheumatoid arthritis, etc. ECs must experience multiple cell division process to grow, and cytokinesis is the final step. The present study shows that PEGylated GNRs (PEG-GNRs) specifically target ECs cytokinesis process which results in high ratio of binucleated cells, and these binucleated ECs lose the ability to proliferate. Further data show that PEG-GNRs do not induce toxicity in vitro and in vivo. PEG-GNRs could inhibit ECs proliferation, migration, tube formation and inhibit angiogenesis in ex vivo model. Oxygen induced retinopathy and tumor angiogenesis model further show that PEG-GNRs can inhibit angiogenesis in vivo. Gene expression profiles reveal that PEG-GNRs mainly affect ECs cell division process, and PEG-GNRs treated ECs are arrested in G2/M phase. The mechanism is that PEG-GNRs could disrupt TGFß pathway, and subsequently suppress the assembly of actin filaments in contractile ring site. These findings indicate that PEG-GNR is a novel cytokinesis inhibitor which can be used to interfere with retinal angiogenesis and tumor.