Activities Toward Biomedical Applications of Detonation Nanodiamonds

Daicel, as a century-old company, has worked on products and services for the medical field over many years. Specifically, we have manufactured several active pharmaceutical ingredients (APIs) and intermediates. In recent years, we launched new products of novel concept such as pre-mixed excipient for orally disintegrating (OD) tablets, as exemplified by “Granfiller-D^TM”, and pyro-drive jet injector “Actranza^TM Lab”.<br/>In the meantime, there have been a lot of publications for biomedical application of nanodiamonds (NDs). Since Daicel have been developing detonation nanodiamond (DND) products, “Dinnovare^TM”, these statements motivate us to pursue our NDs to apply in this field. In the talk, we introduce the following topics as our representative R&D activities related to DNDs.<br/>1. Polyglycerol modified nanodiamonds (DND-PG)<br/>DND-PG have originally been created by Prof. Komatsu in collaboration with Daicel [1]. They are highly dispersible in water of even high ionic concentration and, thereby, promising in various applications. In this context, we have developed manufacturing process of DND-PG for commercial production. As well, we are seeking applications such as nanodrugs for cancer treatment through further precise chemical modification, and exploring unique and prominent dispersive characteristics [2, 3].<br/>2. Fluorescent detonation nanodiamonds (f-DNDs)<br/>Color centers such as nitrogen-vacancy (NV), silicon-vacancy (SiV) and other heteroatom-related centers have been studied by many groups for bio-sensing and imaging. DNDs having color centers are especially desired because of their comparable size to biomolecules, which should be advantageous to trace those molecules in cells. Recently, we successfully synthesized single-digit SiV-DNDs via straightforward detonation process, in which a selected silicon-containing compound was mixed in explosive charge [4]. We are exploring applications of f-DND as well as fabrication of other color centers.<br/>3. Nanometer-scale ordered precise arrangement of DNDs on substrate<br/>We have developed a novel technique to arrange DND particles on a substrate in nanometer-scale [5]. Using the lift-off process combining electron beam lithography and surface functionalization, the static electrical charge of substrate is locally controlled and precise patterning with DND particles by the electrostatic deposition can be achieved. This technique will open the way to nanometer-scale sensors using DNDs.<br/>[1] L. Zhao, T. Takimoto, M. Ito, N. Kitagawa, T. Kimura, and N. Komatsu,<i> Angew. Chem. Int. Ed.</i> <b>2011</b>, <i>50</i>, 1388.<br/>[2] M. Nishikawa, H. G. Kang, Y. Zou, H. Takeuchi, N. Matsuno, M. Suzuki, and N. Komatsu, <i>Bull. Chem. Soc. Jpn.</i> <b>2021</b>, <i>94</i>, 2302.<br/>[3] T. Yoshikawa, M. Liu, S. L. Y. Chang, I. C. Kuschnerus, Y. Makino, A. Tsurui, T. Mahiko and M. Nishikawa, “Steric interaction of polyglycerol-functionalized detonation nanodiamonds”, <i>in press.</i><br/>[4] Y. Makino, T. Mahiko, M. Liu, A. Tsurui, T. Yoshikawa, S. Nagamachi, S. Tanaka, K. Hokamoto, M. Ashida, M. Fujiwara, N. Mizuochi and M. Nishikawa, <i>Diam. Relat. Mater.</i> <b>2021</b>, <i>112</i>, 108248.<br/>[5] T. Yoshikawa, M. Liu, H. Miyake, R. Ieki, R. Kojima, Y. Makino, A. Tsurui, T. Mahiko and M. Nishikawa, <i>Appl. Phys. Express</i> <b>2021</b>, <i>14</i>, 055003.