Research & Initiatives

Our Research Goal

Research interests of Eijiro Miyako's laboratory are in the area of Bioengineering, Materials Chemistry, Nanotechnology and Nanomedicine. In particular, using various physicochemical properties of materials and living organisms, we challenge to develop an innovative "bio symphonic system" that can monitor, control, and orchestrate biological activities at atomic, molecular, or subcellular level for our health, environment, and peace issues. To this end, our work is also focused on the syntheses of high-quality "nano-micro scale robots (nano-microbots)", the engineering of their surface, and their assembly and consolidation into a functional nano-microbot to the aforesaid target biological applications, as well as to develop fundamental understanding of structure-property relationships. We are also concentrating on creating nature-inspired materials and robotic engineering as game-changing technology in the field of food and agricultural industries. The interdisciplinary nature of our research aims for a collaborative team of chemists, physicists, biologists, material scientists, and engineers etc..

(1) Intratumoral Oncolytic Super Bacteria for Cancer Treatment (Advanced Science 23016 (2023).)

Unveiling biomedical functions of tumor-resident microbiota is challenging for developing advanced anticancer medicines. This study demonstrates that isolated intratumoral bacteria, associated with natural purple photosynthetic bacteria, have inherent biocompatibility and strong immunogenic anticancer efficacies. They preferentially grow and proliferate within a targeted tumor milieu, which effectively causes immune cells to infiltrate the tumor and provoke strong anticancer responses in various syngeneic mouse models, including colorectal cancer, sarcoma, metastatic lung cancer, and extensive drug-resistant breast cancer. Furthermore, these functional bacteria-treated mice exhibit excellent anticancerous responses and have significantly prolonged survival rates with effective immunological memory. Light-harvesting nanocomplexes of microbial consortia of intratumoral bacteria and purple photosynthetic bacteria can diagnose tumors using bio-optical-window near-infrared light, making them useful theranostic agents for highly targeted immunological elimination of the tumor and for precisely marking tumor location.

(2) Photosynthetic Bacteria-Based Cancer Optotheranostics (Nano Today 37, 101100 (2021).)

Despite the growing promise of bacterial therapy, due to the tumor targeting effect, in solid tumor treatment, most conventional therapeutic bacteria exhibit pathogenicity and insufficient therapeutic efficacy in the tumor milieu. Here we show the optical characterization of non-pathogenic natural purple photosynthetic bacteria (PPSB), which displays multifunctionality and biocompatibility in the treatment of highly active cancers. To this end, the living PPSB are applied in cancer theranostics, using bio-optical-window I and II near-infrared (NIR) light. PPSB exhibit strong NIR-I-to-NIR-II reporter fluorescence, powerful photothermal conversion, excellent reactive oxygen species generation, and contrasting photo-acoustic effects, via the energy transfer system of light harvesting nanocomplexes in PPSB membranes, making PPSB useful for highly targeted tumor elimination and precisely marking tumor location with the help of immune system. Furthermore, short-term fasting, that can evoke anticancer immunological reactions, could dramatically improve the optical efficacies of the bacterial treatment. Starving-mediated and NIR light-driven PPSB would serve as an effective “all-in-one” theranostic material for use in deep tumor treatments.

(3) Bioelectronic Implant Nanodevice (Angew. Chem. Int. Ed. 50, 12266 (2011).)

There is currently substantial interest in creating bioelectronic devices that can be implanted in and attached to humans for sensing and control of organs and internal systems in order to prolong and improve the quality of life. Herein we developed a new type of implantable bioelectronic device that is operated by laser irradiation from outside the body. Carbon nanotubes (CNTs), which absorb laser light and transform it to thermal energy with high efficiency, are key in the design of this device; the thermal energy is further converted into electrical power with a Seebeck device. The CNT-based photo-thermal-electrical (PTE) converter is unique and has potential in practical use as it can be simply operated by near infrared (NIR) laser irradiation, and can be easily removed or replaced as it is embedded near the skin.

(4) Liquid Metal Nanotransformer (Nature Commun. 8, 15432 (2017).)

Room temperature liquid metals (LMs) represent a class of emerging multifunctional materials with attractive novel properties. We developed that photopolymerized LMs presented a unique nanoscale capsule structure characterized by high water dispersibility and low toxicity. We also demonstrated that the LM nanocapsule generated heat and reactive oxygen species under biologically neutral near-infrared (NIR) laser irradiation. Concomitantly, NIR laser exposure induced a transformation in LM shape, destruction of the nanocapsules, contactless controlled release of the loaded drugs, optical manipulations of a microfluidic blood vessel model and spatiotemporal targeted marking for X-ray-enhanced imaging in biological organs and a living mouse. By exploiting the physicochemical properties of LMs, we achieved effective cancer cell elimination and control of intercellular calcium ion flux. In addition, LMs displayed a photoacoustic effect in living animals during NIR laser treatment, making this system a powerful tool for bioimaging.

(5) Supramolecular Nanotrain (Nature Commun. 3, 1226 (2012).)

Biological network systems, such as inter- and intra-cellular signalling systems, are handled in a sophisticated manner by the transport of molecular information. Over the past few decades, there has been a growing interest in the development of synthetic molecular-transport systems. However, several key technologies have not been sufficiently realized to achieve optimum performance of transportation methods. Here we developed that a new type of supra-molecular system comprising of CNTs and liposomes enabled the directional transport and controlled release of carrier molecules, and allowed an enzymatic reaction at a desired area. The study highlighted important progress that has been made towards the development of biomimetic molecular-transport systems and various lab-on-a-chip applications, such as medical diagnosis, sensors, bionic computers and artificial biological networks.

(6) Photothermic Regulation of Gene Expression (Proc. Natl. Acad. Sci. USA 109, 7523 (2012).)

The development of optical methods to control cellular functions is important for various biological applications. In particular, heat shock promoter-mediated gene expression systems by laser light are attractive targets for controlling cellular functions. However, previous approaches have considerable technical limitations related to their use of UV, short-wavelength visible, and infrared laser light, which have poor penetration into biological tissue. Biological tissue is relatively transparent to light inside the diagnostic window at wavelengths of 650–1,100 nm. We presented a unique optical biotechnological method using carbon nanohorn (CNH) that transforms energy from diagnostic window laser light to heat to control the expression of various genes. We reported that with this method, laser irradiation within the diagnostic window resulted in effective heat generation and thus caused heat shock promoter-mediated gene expression. This study provides an important step forward in the development of light-manipulated gene expression technologies.

(7) Light and Magnetic Field-Driven Nanotransporter (Angew. Chem. Int. Ed. 55, 6476, (2016).)

Cancer is one of the primary causes of death worldwide. A high-precision analysis of biomolecular behaviors in cancer cells at the single-cell level and more effective cancer therapies are urgently required. Here, we developed the development of a magnetically- and near infrared light-triggered optical control method, based on nanorobotics, for the analyses of cellular functions. A new type of nanotransporters, composed of magnetic iron nanoparticles, CNHs, and liposomes, was synthesized for the spatiotemporal control of cellular functions in cells and mice. Our technology will help to create a new state-of-the-art tool for the comprehensive analysis of “real” biological molecular information at the single-cell level, and it may also help in the development of innovative cancer therapies.

(8) Nanomodulator-Mediated Regulation of Cancer Stemness (Nature Commun. 11, 4117 (2020).)

Strategies for eradicating cancer stem cells (CSCs) are urgently required because CSCs are resistant to anticancer drugs and cause treatment failure, relapse and metastasis. Here, we show that photoactive functional nanocarbon complexes exhibit unique characteristics, such as homogeneous particle morphology, high water dispersibility, powerful photothermal conversion, rapid photoresponsivity and excellent photothermal stability. In addition, the present biologically permeable second near-infrared (NIR-II) light-induced nanocomplexes photo-thermally trigger calcium influx into target cells overexpressing the transient receptor potential vanilloid family type 2 (TRPV2). This combination of nanomaterial design and genetic engineering effectively eliminates cancer cells and suppresses stemness of cancer cells in vitro and in vivo. Finally, in molecular analyses of mechanisms, we show that inhibition of cancer stemness involves calcium-mediated dysregulation of the Wnt/β-catenin signalling pathway. The present technological concept may lead to innovative therapies to address the global issue of refractory cancers.

(9) Nanohybrid Butterfly Wing (ACS Nano 7, 8736 (2013).)

Insect wings have many unique and complex nano/microstructures that are presently beyond the capabilities of any current technology to reproduce them artificially. In particular, Morpho butterflies are an attractive type of insect because their multifunctional wings are composed of nano/microstructures. Here we show that carbon nanotube-containing composite adopts honeycombshaped networks when simply self-assembled on Morpho butterfly wings used as a template. The unique nano/microstructure of the composites exhibits multifunctionalities such as laser-triggered remote-heating, high electrical conductivity, and repetitive DNA amplification. Our present study highlights the important progress that has been made toward the development of smart nanobiomaterials for various applications such as digital diagnosis, soft wearable electronic devices, photosensors, and photovoltaic cells.

(10) Materially Engineered Artificial Pollinator (Chem 2, 224 (2017).)

Pollinating insects such as honeybees play a critical role in maintaining the natural environment. The decline in honeybee populations is a global issue with significant repercussions with respect to the pollination of plants. The simultaneous expression of multifunctionality from the synthesized soft ionic liquid gel (ILG) for biotechnology is found in this study. We also demonstrate that, when mixed with photochromic organic compounds, ILGs display rapid color changes on living Musca domestica specimens similar to light-triggered camouflage. By further exploiting the physicochemical properties of ILGs, we could achieve effective pollen adsorption by ILG-functionalized Formica japonica specimens from Tulipa gesneriana flowers with high biocompatibility. In addition, a radio-wave-controllable bioinspired flying robot equipped with ILG-coated vertically aligned animal hairs could be used successfully to pollinate Lilium japonicum flowers. Such materially engineered artificial plant pollinators should lead to the development of high-performance robotics that can help the counter the decline in honeybee populations.

(11) Soap Bubble Pollination (iScience 23, 101188 (2020).)

Natural and artificial flower pollination are critical processes in the life cycle of flowering plants. Declines in the number of global pollinator insects, the heavy labor of conducting artificial pollination manually, and the rising cost of pollen grains are considered to be significant worldwide problems. Here we show that chemically functionalized soap bubbles exhibit effective and convenient delivery of pollen grains to the targeted flowers thanks to their stickiness, softness, high flexibility, and enhancement of pollen activity. By exploring the physicochemical properties of functional soap bubbles, we could prepare mechanically stabilized soap bubbles capable of withstanding the windmills produced by robotic pollination. An unmanned aerial vehicle equipped with a soap bubble maker was autonomously controlled to pollinate flowers. Such technology of automatic intelligent robotic pollination with functional soft materials would lead to innovative agricultural systems that can tackle the global issues of pollination.