Nanogel tectonics engineering

Nanocarrier-Integrated Microspheres: Nanogel Tectonic Engineering for Advanced Drug-Delivery Systems
A nanocarrier-integrated bottom-up method is a promising strategy for advanced drug-release systems. Self-assembled nanogels, which are one of the most beneficial nanocarriers for drug-delivery systems, are tectonically integrated to prepare nanogel-cross-linked (NanoClik) microspheres. From the basic characterizations including the stimulated emission depletion（STED）microscopy, NanoClik microspheres were around 10 micrometer in size and consisted of nanogel-derived structures and released "drug-loaded nanogels" after hydrolysis, resulting in successful sustained drug delivery in vivo. The size controlling in the rage of micrometer and double-layered NanoClik microspheres were accomplished. These findings suggested that a NanoClik microsphere is attractive carrier for drug delivery systems. nanogel Fig.1
Fig.1 Schematic illustration of NanoClik microsphere　　　　　　　　　　　　　　 
Paper
Y. Tahara, S. Mukai, S. Sawada, Y. Sasaki, K. Akiyoshi, Nanocarrier-Integrated Microspheres: Nanogel Tectonic Engineering for Advanced Drug-Delivery Systems, Adv Mater 27 (2015) 5080-5088.
Nanogel tectonic porous gel loading biologics, nanocarriers, and cells for advanced scaffold
We developed a new self-assembled amphiphilic nanogel-crosslinked porous (NanoCliP) gel that can trap proteins, liposomes, and cells. The NanoCliP gel was prepared by Michael addition of a self- assembled nanogel of acryloyl group-modified cholesterol-bearing pullulan to pentaerythritol tetra (mercaptoethyl) polyoxyethylene, followed by freezing-induced phase separation. Dynamic rheological analysis revealed that the storage modulus of the NanoCliP gel was approximately 10 times greater than that of a nonporous nanogel-crosslinked gel. Two-photon excitation deep imaging revealed that the NanoCliP gel comprises interconnected pores of several hundred micrometers in diameter. The NanoCliP gel trapped proteins and liposomes via hydrophobic interactions because its amphiphilic nanogels exhibit chaperone-like activity. Mouse embryonic fibroblasts penetrated the interconnected pores and adhered to the porous surface of fibronectin-complexed NanoCliP gel. In vivo, the NanoCliP gel enhanced cell infiltration, tissue ingrowth, and neovascularization without requiring exogenous growth factors, suggesting that the NanoCliP gel is a promising scaffold for tissue engineering. nanogel Fig.2
Fig.2 Features of NanoClik porous gel
a, b) Reconstructed 3D images of NanoClik porous gel observed by 2-photon LSM.　　　　　　　　 　
Paper
Y. Hashimoto, S. Mukai, S. Sawada, Y. Sasaki, K. Akiyoshi, Nanogel tectonic porous gel loading biologics, nanocarriers, and cells for advanced scaffold, Biomaterials 37 (2015) 107-115.
Glyco Star Polymers as Helical Multivalent Host and Biofunctional Nano-Platform
A series of amylose-based star polymers　as a new glyco biomaterial was synthesized by a click reaction and enzymatic polymerization of specific primers with phosphorylase. The molecular weights were controlled by the enzymatic reaction. Further polymerization resulted in a viscous solution and, especially, for the 8-arm primer, a hydrogel was obtained due to effective cross-linking between the multiarmed structures. The star polymers with a degree of polymerization of about 60 per arm acted as an allosteric multivalent host for hydrophobic molecules by helical formation. A cationic 8-arm star polymer catalyzed DNA strand exchange as a nucleic acid chaperone. Amylose-based star polymers are promising building blocks for producing advanced hybrid glyco biomaterials. nanogel Fig.3
　Fig.3 (top center) Schematic illustration of
　Enzymatic synthesis of the glyco star
　polymer, (left) formation of 　
　supramolecular inclusion complexes, and
　(right) DNA strand exchange reaction.  
Paper
T. Nishimura, S. Mukai, S. Sawada, K. Akiyoshi, Glyco Star Polymers as Helical Multivalent Host and Biofunctional Nano-Platform, Acs Macro Lett 4 (2015) 367-371.
Amylose-Based Cationic Star Polymers for siRNA Delivery
A new siRNA delivery system using a cationic glyco-star polymer is described. Spermine-modified 8-arm amylose star polymer (with a degree of polymerization of approximately 60 per arm) was synthesized by chemoenzymatic methods. The cationic star polymer effectively bound to siRNA and formed spherical complexes with an average hydrodynamic diameter of 230 nm. The cationic 8-arm star polymer complexes showed superior cellular uptake characteristics and higher gene silencing effects than a cationic 1-arm polymer. These results suggest that amylose-based star polymers are a promising nanoplatform for glycobiomaterials. nanogel Fig.4
　　Fig.4 Schematic illustration of the glyco
　　star polymer and CLSM image of the glyco
　　star polymer delivery of Alexa488-labeled
　　siRNA to Renca cells.
Paper
T. Nishimura, K. Umezaki, S.A. Mukai, S. Sawada, K. Akiyoshi, Amylose-Based Cationic Star Polymers for siRNA Delivery, Biomed Res Int 2015 (2015) 962941.