Investigation into the Photochemical Properties of Methylene Blue-Immobilized Hydroxyapatite Nanoparticles for Theranostic Application.

In the biomedical field, there has been a requirement for developing theranostic nanomaterials with higher biosafety, leading to both diagnosis and therapy. Methylene blue (MB+) is an organic dye with both photoluminescence (PL) and photosensitization abilities to generate singlet oxygen (1O2). However, MB+ easily loses its generation ability by hydrogen reduction in vivo or by forming aggregates. In this study, MB+ immobilized on biocompatible hydroxyapatite (HA) nanoparticles was applied for the bifunctions of efficient PL and photosensitization. The MB+-immobilized HA nanoparticles (MH) formed aggregates with sizes of 80-100 nm in phosphate buffer (PB). The generation amount and efficiency of 1O2 from the nanoparticles in PB seem to depend on the immobilized MB+ amount and the percentage of the monomer, respectively. Considering the larger immobilized amount and percentage of the MB+ monomer, it was found that there was MH with the lower generation amount and efficiency of 1O2 to exhibit the highest PL intensity. The photofunctional measurement of MB+ revealed the state of MB+ molecules on the HA surface, and it was suggested that the MB+ molecules immobilized on the MH surface would form more hydrogen bonds to change their excitation states. In the cellular experiments, the Hela cancer cells reacted with the nanoparticles and showed red-color PL, indicating cellular imaging. Furthermore, the adherent cell coverage decreased by 1O2 generation, indicating the importance of the immobilization amount of the MB+ monomer. Therefore, theranostic nanomaterials with biosafety were successfully synthesized to show two photofunctions, which provide both cellular imaging and photodynamic therapy by the nanohybrid system between HA and MB+.

Effective Immobilization of Monomeric Methylene Blue on Hydroxyapatite Nanoparticles by Controlling Inorganic-Organic Interfacial Interactions.

We successfully synthesized methylene blue (MB+)-immobilized hydroxyapatite (HM) nanoparticles by changing the initial P/Ca molar ratio. The immobilized amount of MB+ increased with increasing the initial P/Ca molar ratio from 0.6 to 4.0, and the HM had an elliptical shape (long length, 21-24 nm; short length, 11-13 nm) irrespective of the initial P/Ca molar ratio. Upon increasing the initial P/Ca molar ratio, the number of carbonate ions on the HM surface decreased, which would be owing to the electrostatic repulsion by the surface phosphate ions (i.e., P-O-), the surface P-OH mainly dissociated to form P-O-, and the electrostatic interaction of P-O- with MB+ enhanced. The bonding of MB+ with surface P-OH and Ca2+ sites of hydroxyapatite would be hydrogen-bonding and Lewis acid-base interactions, respectively. The optimum synthesis condition for MB+ immobilization at the monomer state was found to be the initial P/Ca molar ratio of 2.0. Here, the existence percentage of the MB+ monomer and the molecular occupancy of the surface carbonate ion at the initial P/Ca molar ratio of 2.0 were higher than those at 4.0 with no significant difference in the immobilized amount of MB+, indicating that MB+ at the initial P/Ca molar ratio of 4.0 is more aggregated than that at 2.0. These results suggested that a part of carbonate ions has a role as a spacer to suppress MB+ aggregation. Accordingly, the interfacial interactions between the MB+ monomer and the hydroxyapatite surface were clarified, which can effectively be controlled by the initial P/Ca molar ratio. These findings will provide fundamental and useful knowledge for the design of calcium phosphate-organic nanohybrids. We believe that these particles will be the base materials to realize diagnostic and/or therapeutic functions through the molecular state control by optimizing the synthesis conditions.

Study on a practical robotic follower to support home oxygen therapy patients--questionnaire-based concept evaluation by the patients-.

Home oxygen therapy (HOT) is a medical treatment for the patients suffering from severe lung diseases. Although walking outdoors is recommended for the patients to maintain physical strength, the patients always have to carry a portable oxygen supplier which is not sufficiently light weight for this purpose. Our ultimate goal is to develop a mobile robot to carry an oxygen tank and follow a patient in an urban outdoor environment. We have proposed a mobile robot with a tether interface to detect the relative position of the foregoing patient. In this paper, we report the questionnaire-based evaluation about the two developed prototypes by the HOT patients. We conduct maneuvering experiments, and then obtained questionnaire-based evaluations from the 20 patients. The results show that the basic following performance is sufficient and the pulling force of the tether is sufficiently small for the patients. Moreover, the patients prefer the small-sized prototype for compactness and light weight to the middle-sized prototype which can carry larger payload. We also obtained detailed requests to improve the robots. Finally the results show the general concept of the robot is favorably received by the patients.