PMID- 33406818 OWN - NLM STAT- MEDLINE DCOM- 20210302 LR - 20210302 IS - 1944-8252 (Electronic) IS - 1944-8244 (Linking) VI - 13 IP - 3 DP - 2021 Jan 27 TI - Ibandronate-Loaded Carbon Nanohorns Fabricated Using Calcium Phosphates as Mediators and Their Effects on Macrophages and Osteoclasts. PG - 3701-3712 LID - 10.1021/acsami.0c20923 [doi] AB - Carbon nanohorns (CNHs), a type of nanocarbon, have been studied for the application of drug delivery systems (DDSs) because they are easily functionalized, support bone regeneration, can be used to perform photohyperthermia, have low toxicity, and are easily phagocytosed by macrophages. To take advantage of these features of CNHs, we developed a DDS for the local treatment of bone metastasis by loading the antibone resorption drug ibandronate (IBN) onto CNHs. The poor adsorption of IBN onto CNHs due to the weak hydrophilic-hydrophobic interaction was overcome by using calcium phosphates (CaPs) as mediators. In the fabrication process, we used oxidized CNH (OxCNH), which is less hydrophobic, onto which IBN was coprecipitated with CaP from a labile supersaturated CaP solution. OxCNH-CaP-IBN composite nanoparticles exerted stronger cell-suppressive effects than OxCNH and IBN in both murine macrophages (RAW264.7 cells) and osteoclasts (differentiated from RAW264.7 cells). OxCNH-CaP-IBN composite nanoparticles were efficiently phagocytosed by macrophage cells, where they specifically accumulated in lysosomes. The stronger cell-suppressive effects were likely due to intracellular delivery of IBN, i.e., the release of IBN from OxCNH-CaP-IBN composite nanoparticles via dissociation of CaP in the acidic environment of lysosomes. Our findings suggest that OxCNH-CaP-IBN composite nanoparticles are potentially useful for the local treatment of metastatic bone destruction. FAU - Nakamura, Maki AU - Nakamura M AUID- ORCID: 0000-0002-6759-3205 AD - Nanomaterials Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan. FAU - Ueda, Katsuya AU - Ueda K AD - Biomedical Engineering Division, Graduate School of Medicine, Science and Technology, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan. FAU - Yamamoto, Yumiko AU - Yamamoto Y AD - Nanomaterials Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan. FAU - Aoki, Kaoru AU - Aoki K AD - Physical Therapy Division, School of Health Sciences, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan. FAU - Zhang, Minfang AU - Zhang M AUID- ORCID: 0000-0002-3983-3355 AD - CNT Application Research Center, National Institute of Advanced Industrial Science and Technology (AIST), Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan. FAU - Saito, Naoto AU - Saito N AD - Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan. FAU - Yudasaka, Masako AU - Yudasaka M AD - Nanomaterials Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan. AD - Faculty of Science & Technology, Meijo University, 1-501 Shiogamaguchi, Tenpaku-ku, Nagoya, Aichi 468-8502, Japan. LA - eng PT - Journal Article DEP - 20210106 PL - United States TA - ACS Appl Mater Interfaces JT - ACS applied materials & interfaces JID - 101504991 RN - 0 (Bone Density Conservation Agents) RN - 0 (Calcium Phosphates) RN - 0 (Drug Carriers) RN - 0 (Nanotubes, Carbon) RN - UMD7G2653W (Ibandronic Acid) SB - IM MH - Animals MH - Bone Density Conservation Agents/administration & dosage/*pharmacology MH - Calcium Phosphates/chemistry MH - Drug Carriers/*chemistry MH - Ibandronic Acid/administration & dosage/*pharmacology MH - Macrophages/*drug effects MH - Mice MH - Nanotubes, Carbon/*chemistry/ultrastructure MH - Osteoclasts/*drug effects MH - RAW 264.7 Cells OTO - NOTNLM OT - calcium phosphate OT - carbon nanohorns OT - ibandronate OT - macrophage OT - osteoclast EDAT- 2021/01/08 06:00 MHDA- 2021/03/03 06:00 CRDT- 2021/01/07 05:40 PHST- 2021/01/08 06:00 [pubmed] PHST- 2021/03/03 06:00 [medline] PHST- 2021/01/07 05:40 [entrez] AID - 10.1021/acsami.0c20923 [doi] PST - ppublish SO - ACS Appl Mater Interfaces. 2021 Jan 27;13(3):3701-3712. doi: 10.1021/acsami.0c20923. Epub 2021 Jan 6.