pH-Controlled Gas-Generating Mineralized Nanoparticles: A Theranostic Agent for Ultrasound Imaging and Therapy of Cancers

We report a theranostic nanoparticle that can express ultrasound (US) imaging and simultaneous therapeutic functions for cancer treatment. We developed doxorubicin-loaded calcium carbonate (CaCO₃) hybrid nanoparticles (DOX-CaCO₃-MNPs) through a block copolymer templated <i>in situ</i> mineralization approach. The nanoparticles exhibited strong echogenic signals at tumoral acid pH by producing carbon dioxide (CO₂) bubbles and showed excellent echo persistence. <i>In vivo</i> results demonstrated that the DOX-CaCO₃-MNPs generated CO₂ bubbles at tumor tissues sufficient for echogenic reflectivity under a US field. In contrast, the DOX-CaCO₃-MNPs located in the liver or tumor-free subcutaneous area did not generate the CO₂ bubbles necessary for US contrast. The DOX-CaCO₃-MNPs could also trigger the DOX release simultaneously with CO₂ bubble generation at the acidic tumoral environment. The DOX-CaCO₃-MNPs displayed effective antitumor therapeutic activity in tumor-bearing mice. The concept described in this work may serve as a useful guide for development of various theranostic nanoparticles for US imaging and therapy of various cancers

Inhibition of Osteoclast Differentiation by Gold Nanoparticles Functionalized with Cyclodextrin Curcumin Complexes

Gold nanoparticles (GNPs) have been previously reported to inhibit osteoclast (OC) formation. However, previous research only confirmed the osteoclastogenesis inhibitory effect under <i>in vitro</i> conditions. The aim of this study was to develop a therapeutic agent for osteoporosis based on the utilization of GNPs and confirm their effect both <i>in vitro</i> and <i>in vivo</i>. We prepared β-cyclodextrin (CD) conjugated GNPs (CGNPs), which can form inclusion complexes with curcumin (CUR–CGNPs), and used these to investigate their inhibitory effects on receptor activator of nuclear factor-κb ligand (RANKL)-induced osteoclastogenesis in bone marrow-derived macrophages (BMMs). The CUR–CGNPs significantly inhibited the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells in BMMs without inducing cytotoxicity. The mRNA expressions of genetic markers of OC differentiation including c-Fos, nuclear factor of activated T cells 1 (NFATc1), TRAP, and osteoclast associated receptor (OSCAR) were significantly decreased in the presence of CUR–CGNPs. In addition, the CUR–CGNPs inhibited OC differentiation of BMMs through suppression of the RANKL-induced signaling pathway. Additionally, CUR–CGNPs caused a decrease in RANKL-induced actin ring formation, which is an essential morphological characteristic of OC formation allowing them to carry out bone resorption activity. Furthermore, the <i>in vivo</i> results of an ovariectomy (OVX)-induced osteoporosis model showed that CUR–CGNPs significantly improved bone density and prevented bone loss. Therefore, CUR–CGNPs may prove to be useful as therapeutic agents for preventing and treating osteoporosis