| POLYMERS Vol.65 No.8 |
| >> Japanese | >> English |
COVER STORY
“Intelligent” Stimuli-Responsive Water Soluble Polymers |
| COVER STORY: Highlight Reviews |
| Development of Stimuli Responsible Water-Soluble Functional Polymers for Biomedical Purpose: Creating Ischemia Cell Specific Oligonucleotide Therapeutics System with Environment-Responsive Peptide Ribonucleic Acids (PRNAs) | Takehiko WADA |
| <Abstract> We have reported a series of novel artificial nucleic acids, named Peptide Ribonucleic Acids (PRNAs), as promising candidates for ischemic/hypoxic cell specific oligonucleotide therapeutics. PRNAs are consisted with γ- and/or α-glutamate peptide backbone and 5’-amino ribonucleoside moiety in the side chain. For applying ischemic/hypoxic cell specificificity, PRNAs containing phenylboronic acid moiety with appropriate substients (PRNA-PBA) were synthesized. Under the normal cellular condition (pH≒7.2), the PRNA-PBA unit forms intramolecular cyclic borate ester with 2’,3’-cis-diole of PRNA’s furanose residue, and then PRNA’s nucleobase preferres syn orientation, which is no recognition/complexation ability with any nucleobases of RNA and/or DNA. On the other hand, under the ischemic/hypoxic cellular conditions (pH 6.2～5.8), the pH triggered nucleobase-orientation switching of PRNA from syn to anti is induced by dissociation of the borate ester and then anti oriented nuclobases of PRNAs recognize and form stable complex with target functional RNA, which is an essential function of oligonucleotide therapeutics strategy. Therefore, PRNAs expect to be intracellular environment condition responsible artificial nucleic acids for oligonucleotide therapeutics strategy, and then can discriminate ischemic/hypoxic cells and normal cell. Keywords: Stimli Responsible / pH Responsible / Oligonucleotide Therapeutics / Cancer Cell Spesific / Ischemia / Artificial Nucleic Acid / Orientation Control / Recognition Control |
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| Drug Delivery System Controlled by Near-Infrared Light | Takuro NIIDOME |
| <Abstract> The control technique of drug delivery systems by external stimuli is an important key for improving its efficiency and reducing undesirable side effects of the drug. Near-infrared light, alternating magnetic field and ultrasound, etc. are used as external stimuli, and each stimulus has its specific advantage. Among them, near-infrared light has the advantage that it can penetrate deeply into tissue and focus on a specific region. Therefore, many delivery systems that are controlled by near-infrared light have been reported in literature. In order to control the drug delivery by near-infrared light irradiation as a trigger, gold nanoparticles that have absorption band at near-infrared light are employed. Such gold nanoparticles can be heated up by the light irradiation, the so-called photothermal effect. By a combination of thermo-responsive polymers with drugs and the nanoparticles, drug release can be controlled by the light irradiation. The nanoparticles themselves can be also accumulated at the irradiated site. These smart drug delivery systems that are combined with external stimuli will be powerful medical tools in the next generation. Keywords: Drug Delivery / Gold Nanoparticles / Near-Infrared Light |
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| Magnetoresponsive Nanohybrid Materials for Potential Biomedical Applications | Kiyofumi KATAGIRI, Yoshihiro SASAKI |
| <Abstract> The magnetic field is one of the most versatile candidates as an external stimulus for biomedical applications since it can penetrate deeply into biological tissues. In this highlight review, we introduce nanohybrid materials formed with soft materials, e.g., lipid bilayer membranes and polysaccharide nanogels, and magnetic nanoparticles (NPs) for biomedical applications. Magnetoliposomes, i.e., lipid bilayer vesicles embedded with magnetite NPs were developed for magnetic force-based tissue engineering, magnetic hyperthermia therapy, and drug delivery systems. Magnetoliposomes conjugated with thermoresponsive polymers have on-demand release functions upon alternating magnetic field (AMF) irradiation. In this hybrid system, heating of magnetic NPs via AMF irradiation triggered morphological change of the thermoresponsive polymer. Nanohybrid materials formed with polysaccharide nanogels and magnetic NPs were also developed. These nanohybrids were applicable as MRI contrast agents and in magnetic hyperthermia as well. In addition, these nanohybrids also have potentials for the magnetically guided protein transduction. Keywords: Magnetic Nanoparticles /Lipid Bilayer / Polysaccharide Nanogels / Drug Delivery Carrier / Hyperthermia Therapy / Protein Transduction |
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| COVER STORY: Topics and Products |
| Stimulation-Responsive Structural Change of Water-Soluble Polyanilines | Toru AMAYA, Toshikazu HIRAO |
| <Abstract> Stimulation-responsive structural change of water-soluble polyanilines is described. A self-doped polyaniline, poly(2-methoxyaniline-5-sulfonic acid) (PMAS), exhibits the reversible structural switching in aqueous solution, which is considered to be induced by the partial redox reaction. Another self-doped polyaniline, poly(2-methoxyaniline-5-phosphonic acid) (PMAP) developed in our group, shows the deprotonation-induced delocalization of the polaron in aqueous solution, which can be accounted for by partial streching of the main chain. Keywords: Polyaniline / Doping / Conducting Polymer / PMAP / Structural Change |
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| Ureido Polymers Showing UCST-Type Phase Separation Behavior | Naohiko SHIMADA, Atsushi MARUYAMA |
| <Abstract> Ureido polymers exhibit UCST-type phase separation behavior under physiologically relevant conditions. Phase separation temperature can be controlled by changing molecular weight or ureido contents. Notably, we showed that ureido polymers having 10 mol% ionic groups still exhibited UCST behavior. This property of ureido polymers expands their usefulness as biomaterials. We examined capture and separation of particular proteins from a protein mixture by cooling-induced phase separation. Thermal denaturation and damage to proteins can be minimized. Selective and rapid capture of particular proteins from protein mixture by ureido polymers having ionic groups was shown. Interestingly, cells in monolayer cultures were converted to spheroids by the addition of ureido polymers. The spheroid/monolayer culture was repeatably changed by changing culture temperature. Keywords: Temperature Responsive Polymers / UCST / Physiolgical Conditions / Biomaterials |
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| Target Molecule-Responsive Gel Particles | Akifumi KAWAMURA |
| <Abstract> Stimuli-responsive gels that undergo changes in size in response to external stimuli have attracted considerable attention. We have prepared molecule-responsive hydrogels by using molecular complexes as dynamic crosslinks. In this paper, we describe the glucose and bisphenol A (BPA)-responsive gel particles that undergo changes in size in response to target glucose or BPA. The glucose responsive gel particles prepared by soap-free emulsion polymerization recognized target glucose and swelled rapidly owing to the dissociation of GEMA-ConA complexes acting as dynamic crosslinks. We also prepared organic-inorganic hybrid nanoparticles with BPA-responsive hydrogel layer on the surface of SiO2 nanoparticles by surface-initiated atom transfer radical polymerization. The resulting CD-PAAm/SiO2 underwent a change in size in response to BPA owing to an increase in the crosslinking density of the CD-PAAm hydrogel layer, resulting from the formation of CD-BPA-CD complexes acting as dynamic crosslinks. The smart functions of molecule-responsive gel particles can provide useful tools for constructing carriers for drug delivery systems and molecular sensors. Keywords: Stimuli-Responsive Gel Particle / Molecule-Respinsive Gel Particle / Dynamic Crosslink / Surfactant-Free Emulsion Polymerization / Surface-Initiated Atom Transfer Radical Polymerization / Drug Delivery System / Molecular Sensor |
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| Polymer Science and I: A Personal Account |
| Young Scientist’s Manners | Keiji NUMATA |
| <Abstract> In this short essay, the definition, advantage and disadvantage of being a young scientist are summarized according to the author’s experiences including Tokyo Young Polymer Scientists’ activities. The struggling young scientist introduces one bitter and fantastic story with starting up his own castle. |
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| Front-Line Polymer Science |
| Cutting Edge of DDS Research for Immunotherapy | Eiji YUBA, Atsushi HARADA, Kenji KONO |
| <Abstract> Cancer immunotherapy has gained much attention because of high selectivity, low side effects, and safety. To achieve efficient cancer immunotherapy, the induction of antigen-specific cytotoxic T lymphocytes (CTLs) is crucial because CTLs can directly kill tumor cells. For the induction of CTLs, the selective delivery of tumor antigen to dendritic cells (DCs) in skin tissues or lymph nodes, the activation of DCs, and the induction of cross presentation of tumor antigen on DCs are necessary. In addition, the depletion of immunosuppressive cells in tumor tissues, such as myeloid-derived suppressor cell and regulatory T cells, is required to avoid the suppression of CTLs in tumor. In this review, state-of-art studies on polymer-based accurate delivery systems of antigen, which can deliver antigen to DCs in skin and/or lymph nodes, induce the cross-presentation of exogenous antigen, activate DCs and suppress the immunosuppressive cells in tumor, are outlined. Keywords: Cancer Immunotherapy / Dendritic Cell / Lymph Node / Antigen / Cross Presentation / Cytotoxic T Lymphocyte |
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