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3. Functional collagen materials

  3-1. Thermal-responsive collagen materials (Figure 7)

Collagen is the most abundant protein in animals and has been used as a biomaterial for a long time. Collagen materials have previously been prepared as DDS materials and used as extended-release materials. In our research, we are preparing hybrid materials of dendrimer and collagen for the purpose of preparing collagen materials that can control dug release. It is known that collagen has repeat sequences consisting of glycine-proline-(hydroxyl)proline and function in the body by forming a triple helix. As such, we used the repeat sequences as collagen model peptides, and bound this to the end groups of dendrimer, which is a useful drug carrier. We then found that collagen model peptide did not only form a triple helix, but could also be induced to form a triple helical structure by accumulating with end groups of dendrimer. In addition, we found that the triple helical structure changed reversibly in response to temperature. This property is not found in native collagen. This thermal reversibility can contribute to the preparation of hydrogel and many possible applications in the controlled release of drugs responsive to temperature.

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  • Kojima et al, Chem. Lett., 40, 1249 (2011).
  • Kojima et al, Soft Matter, 7, 8991 (2011).
  • Suehiro et al, Biopolymers, 95, 270 (2011).
  • Suehiro et al, Biopolymers, 93, 640 (2010).
  • Kojima et al, J. Am. Chem. Soc., 131, 6052 (2009).

  

Collagen dendrimer

Fig. 7. Collagen dendrimer.

  

  3-2. Collagen materials responding to cancer metastasis

Metastasis is peculiar to cancer and occurs with degradation of the extracellular matrix. In this study, we designed functional collagen gels bearing a drug carrier with an anticancer drug. In this system, substances could be released from the gels in response to the secretion of matrix metalloproteinases (MMP) from metastatic carcinoma. We prepared collagen gels with various drug carriers, such as dendrimer and polypeptide carrying the anticancer drug adriamycin via hydrazone linkages. We examined the cytotoxicity of these gels against invasive and noninvasive breast cancer cells.

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  • Kojima et al, Acta Biomaterialia, 9, 5673 (2013).
  • Watanabe et al, Int. J. Pharm., 446, 81 (2013).
  • Kojima et al, Nanomedicine, 9, 767 (2013).

  

Design of metastasis-associated DDS

Fig. 8. Design of metastasis-associated DDS.