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Katsutoshi Kokubun,1,2 Sachiko Matsumura,1 Masako Yudasaka,3,4 Sumio Iijima,3,4 Kiyotaka Shiba1 1Division of Protein Engineering, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan; 2Department of Clinical Pathophysiology, Tokyo Dental College, Tokyo, Japan; 3Nanomaterials Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Japan; 4Graduate School of Science and Technology, Meijo University, Nagoya, Japan Introduction: Inorganic materials are widely used in medical devices, such as artificial hearts, vessels, and joints, in stents, and as nanocarriers for drug-delivery systems. Carbon nanomaterials are of particular interest due to their biological inertness and their capability to accommodate molecules. Several attempts have been proposed, in which carbon nanomaterials are used as nanocarriers for the systemic delivery of drugs.Materials and methods: We developed a drug-delivery system in which oxidized single-walled carbon nanohorns (oxSWNHs) were immobilized on a titanium (Ti) surface using material-binding peptides to enable localized drug delivery. For this purpose, we utilized a bispecific peptidic aptamer comprising a core sequence of a Ti-binding peptide and a SWNH-binding peptide to immobilize oxSWNHs on Ti.Results: Scanning electron microscopy was used to confirm the presence of oxSWNHs adsorbed onto the Ti surface, and a quartz crystal microbalance was used to evaluate the binding process during oxSWNH adsorption. The oxSWNHs-ornamented Ti substrate was nontoxic to cells and released biologically active dexamethasone over a sustained period.Conclusion: This oxSWNHs-immobilized system can be used to modify the surface of Ti in implants and be loaded with drugs that stimulate osteogenesis and bone regeneration. Keywords: drug carrier, drug delivery, carbon nanomaterial, carbon nanohorn, peptide aptamer

Tooth loss is prevalent in older adults and associated with functional capacity decline. Studies on the susceptibility of some individuals to the effects of tooth loss are lacking. This study aimed to investigate the heterogeneity of the association between tooth loss and higher-level functional capacity in older Japanese individuals employing a machine learning approach. This is a prospective cohort study using the data of adults aged ≥65 y in Japan (N = 16,553). Higher-level functional capacity, comprising instrumental independence, intellectual activity, and social role, was evaluated using the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC). The scale ranged from 0 (lowest function) to 13 (highest function). Doubly robust targeted maximum likelihood estimation was used to estimate the population-average association between tooth loss (having <20 natural teeth) and TMIG-IC total score after 6 y. The heterogeneity of the association was evaluated by estimating conditional average treatment effects (CATEs) using the causal forest algorithm. The result showed that tooth loss was statistically significantly associated with lower TMIG-IC total scores (population-average effect: −0.14; 95% confidence interval, −0.18 to −0.09). The causal forest analysis revealed the heterogeneous associations between tooth loss and lower TMIG-IC total score after 6 y (median of estimated CATEs = −0.13; interquartile range = 0.12). The high-impact subgroup (i.e., individuals with estimated CATEs of the bottom 10%) were significantly more likely to be older and male, had a lower socioeconomic status, did not have a partner, and had poor health conditions compared with the low-impact subgroup (i.e., individuals with estimated CATEs of the top 10%). This study found that heterogeneity exists in the association between tooth loss and lower scores on functional capacity. Implementing tooth loss prevention policy and clinical measures, especially among vulnerable subpopulations significantly affected by tooth loss, may reduce its burden more effectively. [ABSTRACT FROM AUTHOR]

Sachiko Matsumura,1 Ryota Yuge,2 Shigeo Sato,3 Akihiro Tomida,3 Toshinari Ichihashi,2 Hiroshi Irie,4 Sumio Iijima,2,5,6 Kiyotaka Shiba,1 Masako Yudasaka6 1Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan; 2Smart Energy Research Laboratories, NEC Corporation, Tsukuba, Japan; 3Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan; 4Teikyo University School of Medicine, Tokyo, Japan; 5Faculty of Science and Technology, Meijo University, Tenpaku, Nagoya, Japan; 6Nanotube Research Center, National Institute of Advanced Industrial Science and Technology, Higashi, Tsukuba, Japan Abstract: Nanocarbons have many potential medical applications. Drug delivery, diagnostic imaging, and photohyperthermia therapy, especially in the treatment of tumors, have attracted interest. For the further advancement of these application studies, the microscopic localization of nanocarbons in tumor tissues and cells is a prerequisite. In this study, carbon nanohorns (CNHs) with sizes of about 100 nm were intravenously injected into mice having subcutaneously transplanted tumors, and the CNHs in tumor tissue were observed with optical and electron microscopy. In the tumor tissue, the CNHs were found in macrophages and endothelial cells within the blood vessels. Few CNHs were found in tumor cells or in the region away from blood vessels, suggesting that, under these study conditions, the enhanced permeability of tumor blood vessels was not effective for the movement of CNHs through the vessel walls. The CNHs in normal skin tissue were similarly observed. The extravasation of CNHs was not so obvious in tumor but was easily found in normal skin, which was probably due to their vessel wall structure difference. Proper understanding of the location of CNHs in tissues is helpful in the development of the medical uses of CNHs. Keywords: ultrastructural localization, carbon nanohorn, tumor, in vivo, extravasation