Nano Medical Engineering Laboratory

Outline

The aim of our laboratory is to create new functional materials by a new method which will be developed from a combination of chemical and biotechnological methodologies. We use combinatorial chemistry, molecular engineering, polymer engineering, hybrid materials engineering, gene and protein engineering, micro-fabrication technology, and nanotechnology to synthesize new materials and the systems for development of regenerative medicine, artificial organs, drug delivery systems, nano-medicine, biochips, bioelectronics, artificial enzymes and artificial antibodies.

Our research subjects are the following: (1) Diagnosis by nano-medical engineering: (i) Development of microarray biochips; (ii) Development of molecular sensors working in living cells; (2) Therapy by nano-medical engineering: (i) Preparation of stem cells for regenerative medicine; (ii) Synthesis of fusion protein for regenerative medicine; (iii) RNA interference method using a chemically modified RNA molecule; (iv) Bio-adhesive derived from biopolymers; (3) Creation of functional molecules by synthetic biology(i) Synthesis of photo-responsive aptamers; (ii) Development of catalysts for organic synthesis; (iii) Development of novel in vitro selection systems for creation of functional peptides; 4) Fundamental investigation of soft nanotechnology: (i) Synthesis of polymer carrying zwitterions for anti-biofouling surfaces; (ii) Creation and application of stimulus-responsive polymers.

Recent Research Topic

Medical engineering using nanotechnology

Fig. 1 Micropatterning of protein by photo-lithography and cells on the surface

Above: photo-mask; middle: micropatterned protein (CBB staining); below: cell culture.

We investigate nanomedicine using nanotechnology and chemical technology. One of the research targets is biocompatibility of artificial organs. Although many types of artificial organs have been realized, there are still problems that must be solved, such as surface biocompatibility. The regulation of the interfaces between artificial materials and tissue or blood is a very important factor. Therefore, we added some biological activity on the artificial materials by chemical immobilization of growth factor proteins and preparation of a recombinant growth factor that has a binding activity.

Micropatterning of various biopolymers, including proteins, has been achieved by our laboratory. We have also developed bio-adhesives using biological components consisting of protein or polysaccharide. As a nucleic acid drug, our laboratory developed a dumbbell-shaped RNA which has RNAi activity and reduces biodegradation. In addition, nano-structured RNAs with new functions have been developed. A gene- or protein-triggered pro-drug type drug delivery system is also one of our research targets.

For diagnostic applications of nanomedicine, we developed a new type of micro-array biochip. Using a photo-immobilization technique, it was possible to immobilize various types of organic materials on a substrate. We showed that the microarray biochips were applicable for diagnosis of allergies or auto-immune diseases by comparing results with a traditional method. In addition to the biochip preparation, an automated microarray biochip reader was also developed for clinical application, which will develop into a new method of clinical diagnosis in the future. Visualization of cellular gene expression and sorting of cells by gene expression are also our research targets. For visualization of glutathion transferase in a cell, a new fluorogenic imaging probe was successfully synthesized in our laboratory in collaboration with the Karolinska Institute, Sweden.

Fig. 2 Nano-structured RNAs of RNAi

Fig. 3 Synthesized probes and cellular imaging of glutathione transferase (GST) by the probe

Above: fluorogenic probes for GST; below left: the fluorescence spectra; below right: human breast cancer cell image.

Fig. 3

Reproduced, with permission, from T. Kitajima, S. Obuse, T. Adachi, M. Tomita, Y. Ito, Recombinant human gelatin substitute with photoreactive properties for cell culture and tissue engineering, Biotechnol. Bioeng. 2011, 108, 2468 © (2012) Wiley