Analysis of biomolecules using cyto-responsive supramolecular polymers

Biological systems including cells and tissues are sophisticatedly hierarchical and dynamic, and they always inspire us to design materials for the possible applications. These structures are basically constructed from the building-blocks via several intermolecular forces such as van der Waals interaction, intermolecular hydrogen bonds, electrostatic interaction, and sometimes hydrophobic effects in water, and are directly related to performing a variety of functions such as intercellular signal transduction through plasma membranes, intracellular metabolism triggered by cytoplasmic calcium increase, and cellular proliferations. In the last quarter century, many scientists have studied interfacial phenomena between these biological systems and artificial materials surfaces in order to design functional biomaterials for medical uses. Throughout these researches, it has been well recognized that biological responses to these surfaces include complicated acute and chronic reactions, eventually leading to cellular and tissue rejection in living bodies. In order to solve these problems, one may understand and realize any differences in the structures and their functions between natural tissues and artificial materials. From this point of view, it should be stated that one of the dominant differences would be the mobility of molecules constructing these materials, and quite a new approach is strongly required to design biomaterials which can perform far-reaching properties in future advancing nanomedicines.

In these perspectives, we have studied supramolecular-structured polyrotaxanes as novel biomaterials, because many cyclic molecules are expected to move along a threading polymer chain. One of the characteristics seen in polyrotaxanes is the mobility of cyclic compounds, and they can be freely rotational and sliding if any intermolecular forces with the linear chain and the neighboring cyclic compound are eliminated. In particular, polyrotaxanes consisting of α-CD molecules and a poly(ethylene glycol) (PEG) chain are feasible in the structural components as biomaterials.

In this study, we prepared a variety of cytocleavable and/or ligand-immobilized polyrotaxanes to examine interaction with cells in terms of (1) extracellular bindings with proteins, nucleic acids, and/or lipid membranes, (2) intracellular reactions with proteins in endosomes/lysosomes and/or cytoplasm, (3) cytotoxicity, and (4) delivering proteins and/or nucleic acids to cytoplasm or nucleus of target cells.

Publications

Y. Yamada, M. Hashida, T. Nomura, H. Harashima, Y. Yamasaki, K. Kataoka, A. Yamashita, R. Katoono, N. Yui, Different mechanisms for nanoparticle formation between pDNA and siRNA using polyrotaxane as the polycation, ChemPhysChem 13, in press (2012).
Y. Yamada, T. Nomura, H. Harashima, A. Yamashita, N. Yui, Quantitative and mechisim-based investigation of post-nuclear gene delivery events for transgene expression by biocleavable polyrotaxanes with well controlled cationic density, Biomaterials 33, in press (2012).