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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.

Purpose Multiwalled carbon nanotubes (MWCNTs) have been known to enter the circulatory system via the lungs from inhalation exposure; however, its carcinogenicity and subsequent accumulation in other organs have not been adequately reported in the literature. Moreover, the safety of MWCNTs as a biomaterial has remained a matter of debate, particularly when the material enters the circulatory system. To address these problems, we used carcinogenic rasH2 transgenic mice to intravenously administer highly dispersed MWCNTs and to evaluate their carcinogenicity and accumulation in the organs. Methods Two types of MWCNTs (thin- and thick-MWCNTs) were intravenously administered at a high dose (approximately 0.7 mg per kg body weight) and low dose (approximately 0.07 mg per kg body weight). Results MWCNTs showed pancreatic accumulation in 3.2% of mice administered with MWCNTs, but there was no accumulation in other organs. In addition, there was no significant difference in the incidence of tumor among the four MWCNTs-administered groups compared to the vehicle group without MWCNTs administration. Blood tests revealed elevated levels in mean red blood cell volume and mean red blood cell hemoglobin level for the MWCNTs-administered group, in addition to an increase in eotaxin. Conclusion The present study demonstrated that the use of current technology to sufficiently disperse MWCNTs resulted in minimal organ accumulation with no evidence of carcinogenicity.

One of the greatest challenges to overcome in the pursuit of the medical application of carbon nanomaterials (CNMs) is safety. Particularly, when considering the use of CNMs in drug delivery systems (DDSs), evaluation of safety at the accumulation site is an essential step. In this study, we evaluated the toxicity of carbon nanohorns (CNHs), which are potential DDSs, using human lymph node endothelial cells that have been reported to accumulate CNMs, as a comparison to fibrous, multi-walled carbon nanotubes (MWCNTs) and particulate carbon black (CB). The effect of different surface characteristics was also evaluated using two types of CNHs (untreated and oxidized). In the fibrous MWCNT, cell growth suppression, as well as expression of inflammatory cytokine genes was observed, as in previous reports. In contrast, no significant toxicity was observed for particulate CB and CNHs, which was different from the report of CB cytotoxicity in vascular endothelial cells. These results show that (1) lymph endothelial cells need to be tested separately from other endothelial cells for safety evaluation of nanomaterials, and (2) the potential of CNHs as DDSs., Article, NANOMATERIALS. 10(7):1374 (2020)

Introduction: Carbon nanotubes (CNTs) have various shapes, including needle-like shapes and curled shapes, and the cytotoxicity and carcinogenicity of CNTs differ depending on their shapes and surface modifications. However, the biological responses induced by CNTs and related mechanisms according to the dispersion state of CNTs have not been extensively studied.Materials and methods: We prepared multiwalled CNTs (MWCNTs) showing different dispersions and evaluated these MWCNTs in RAW264 cells to determine cytotoxicity, cellular uptake, and immune responses. Furthermore, RAW264 cells were also used to compare the cellular uptake and cytotoxicity of fibrous MWCNTs and spherical carbon nanohorns (CNHs) exhibiting the same degree of dispersion.Results: Our analysis showed that the cellular uptake, localization, and inflammatory responses of MWCNTs differed depending on the dispersion state. Moreover, there were differences in uptake between MWCNTs and CNHs, even showing the same degree of dispersion. These findings suggested that receptors related to cytotoxicity and immune responses differed depending on the aggregated state of MWCNTs and surface modification with a dispersant. Furthermore, our results suggested that the receptors recognized by the cells differed depending on the particle shape.Conclusion: Therefore, to apply MWCNTs as a biomaterial, it is important to determine the carcinogenicity and toxicity of the CNTs and to examine different biological responses induced by varying shapes, dispersion states, and surface modifications of particles., Article, INTERNATIONAL JOURNAL OF NANOMEDICINE. 13:6079-6088(2018)

We evaluated starfish-derived &beta, tricalcium phosphate (Sf-TCP) obtained by phosphatization of starfish-bone-derived porous calcium carbonate as a potential bone substitute material. The Sf-TCP had a communicating pore structure with a pore size of approximately 10 &mu, m. Although the porosity of Sf-TCP was similar to that of Cerasorb M (CM)&mdash, a commercially available &beta, TCP bone filler&mdash, the specific surface area was roughly three times larger than that of CM. Observation by scanning electron microscopy showed that pores communicated to the inside of the Sf-TCP. Cell growth tests showed that Sf-TCP improved cell proliferation compared with CM. Cells grown on Sf-TCP showed stretched filopodia and adhered, cells migrated both to the surface and into pores. In vivo, vigorous tissue invasion into pores was observed in Sf-TCP, and more fibrous tissue was observed for Sf-TCP than CM. Moreover, capillary formation into pores was observed for Sf-TCP. Thus, Sf-TCP showed excellent biocompatibility in vitro and more vigorous bone formation in vivo, indicating the possible applications of this material as a bone substitute. In addition, our findings suggested that mimicking the microstructure derived from whole organisms may facilitate the development of superior artificial bone.

Many biomaterials have been evaluated using cultured cells. In particular, osteoblast-like cells are often used to evaluate the osteocompatibility, hard-tissue-regeneration, osteoconductive, and osteoinductive characteristics of biomaterials. However, the evaluation of biomaterial osteogenesis-inducing capacity using osteoblast-like cells is not standardized; instead, it is performed under laboratory-specific culture conditions with different culture media. However, the effect of different media conditions on bone formation has not been investigated. Here, we aimed to evaluate the osteogenesis of MC3T3-E1 cells, one of the most commonly used osteoblast-like cell lines for osteogenesis evaluation, and assayed cell proliferation, alkaline phosphatase activity, expression of osteoblast markers, and calcification under varying culture media conditions. Furthermore, the various media conditions were tested in uncoated plates and plates coated with collagen type I and poly-L-lysine, highly biocompatible molecules commonly used as pseudobiomaterials. We found that the type of base medium, the presence or absence of vitamin C, and the freshness of the medium may affect biomaterial regeneration. We posit that an in vitro model that recapitulates in vivo bone formation should be established before evaluating biomaterials., Article, International Journal of Molecular Sciences. 22(14):7752 (2021)

A design of novel synthetic polymers possessing metallic properties is studied on the basis of the one-dimensional tight-binding self consistent field-crystal orbital (SCF-CO) method. The idea presented here is to utilize crossing π bands of polyperylene (PP) and poly(p-phenylene) (PPP) by controlling the number of π electrons in the polymer skeletons. It is suggested that nitrogen-substituted PP, nitrogen-substituted PPP and boron-substituted PPP can be candidates for showing intrinsic metallic properties.

The electronic structures of polyacenacene (PAA) and its geometrical isomer, polyphenanthrophenanthrene (PPhP) have been studied using the tight-binding SCF-CO (self consistent field-crystal orbital) method with respect to a design of one-dimensional (1D) graphite. The geometry of each polymer is optimized from the energetic point of view. It has been found that from the analysis of the electronic structure of its optimized geometry, PAA favours the structure without the carbon-carbon bond alternations, yielding no band gap. In this sense, PAA is a typical 1D-graphite. On the other hand, it is predicted that the magnitude of the band gap of PPhP in its optimized geometry is almost equal to that of trans -polyacetylene.