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2. Preparation of stimuli-responsive polymer materials

Stimuli-responsive materials are useful as drug delivery system (DDS) materials to pinpoint the release of a drug. So, we are attempting to prepare polymer materials to use with various stimuli, using dendrimers and hyperbranched polymers.

  

  2-1. Photo-responsive materials

In the medical field, optical technology has a long history (e.g. X-rays). Recently, the development of medical technology aiming to improve the quality of life (QCL) has been investigated actively. In particular, much research has focused on non-invasive, or low-invasive medical care to reduce pain in treatment. Low toxicity-gold nanoparticles have been examined as a photo-responsive material. Gold nanoparticles can absorb light from the visible to the near-infrared part of the spectrum, and convert it to thermal energy. Therefore, we can perform selective treatment in affected areas by delivering gold nanoparticles and irradiating with light. As such, we are currently preparing gold nanoparticles using the PEG-modified dendrimer as a template (Figure 5). Using PEG-modified dendrimer, we have found that it is possible to deliver gold nanoparticles to affected areas. In addition, we are preparing gold nanoparticles in various conditions for use as photo-responsive materials that respond to light of various wavelengths.
Au NP-loaded PEGylated dendrimers have been also studied as a contrast agent for X-ray CT.

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  • Kojima, et al, Colloids and Surf. B: Biointerfaces, 81, 648 (2010).
  • Umeda, et al, Bioconjugate Chem., 21, 1559 (2010).
  • Kojima, et al, Nanotechnology, 21, 245104 (2010).
  • Haba, et al, Langmuir, 23, 5243 (2007).

  

Preparation of gold nanoparticle-encapsulated dendrimer

Figure 5. Preparation of gold nanoparticle-encapsulated dendrimer.

  

  2-2. Thermal- and pH-responsive materials (Figure 6)

In the human body, it is known that temperature can be controlled by hyperthermia. Also, pH is different between tissue and subcellular organelles. Materials that respond to temperature and pH are very useful as DDS materials because they are easy to control in the body. A range of different materials have been investigated previously for this purpose. We selected hyperbranched polymers of polyglycerol to use as a polymer backbone, because it is easier to synthesize and has higher biocompatibility than dendrimers. In addition, by bonding carboxyl groups as pH-responsive sites and N-isopropylamide (NIPAm) groups as thermal-responsive sites to end hydroxyl groups of polyglycerol, we synthesized functional polymers that respond to temperature and pH. By optimizing the structure of bonding molecules, we are now preparing molecules that respond to temperature around 37°C.

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  • Kojima, et al, J. Polym. Sci. Part A: Polym. Chem., 48, 4047 (2010).
  • Kojima, et al, Bioconjugate Chem., 20, 1054 (2009).

  

pH/thermal-responsive polymer using polyglycerol

Figure 6. pH/thermal-responsive polymer using polyglycerol.