The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Kazunari Akiyoshi - One of the best experts on this subject based on the ideXlab platform.
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Nanogel integrated ph responsive composite hydrogels for controlled drug delivery
ACS Biomaterials Science & Engineering, 2017Co-Authors: Gunce E Cinay, Kazunari Akiyoshi, Yoshihiro Sasaki, Pelin Erkoc, Mohammad Alipour, Yoshihide Hashimoto, Seda KizilelAbstract:A novel pH-sensitive hydrogel system consisting of poly(methacrylic acid-g-ethylene glycol) (P(MAA-g-EG)) and acryloyl group modified-cholesterol-bearing pullulan (CHPOA) Nanogels was developed for the controlled delivery of an anticonvulsant drug, pregabalin (PGB). Here, the hydrophilic hydrogel network provides the pH-sensitive swelling behavior, whereas Nanogel components form separate reservoirs for the delivery of drugs with different hydrophobicities. These nanocarrier-integrated hybrid gels were synthesized through both surface-initiated and bulk photopolymerization approaches. The swelling and drug release behavior of these pH-responsive hydrogels synthesized by different photopolymerization approaches at visible and UV light wavelenghts were studied at acidic and basic pH values. Nanogel-integrated hydrogels exhibited higher swelling behavior compared to plain hydrogels in reversible swelling experiments. Similarly, the presence of Nanogels in hydrogel network enhanced the loading and release per...
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self assembled Nanogels of cholesterol bearing hydroxypropyl cellulose a thermoresponsive building block for Nanogel tectonic materials
Langmuir, 2016Co-Authors: Yoshiro Tahara, Yoshihiro Sasaki, Mizuki Sakiyama, Shigeo Takeda, Tomoki Nishimura, Sadaatsu Mukai, Shinichi Sawada, Kazunari AkiyoshiAbstract:Hydroxypropyl cellulose (HPC) is a fascinating polysaccharide to use in developing a Nanogel to be a thermoresponsive building unit for Nanogel tectonic materials. Cholesterol-bearing HPC (Ch-HPC) self-assembled to form Nanogels through hydrophobic interactions of the cholesteryl groups in water. Ch-HPC Nanogels had a lower critical solution temperature in line with that of native HPC. The particle size of Ch-HPC Nanogels was reversibly controlled by the temperature and salting-out effect. The thermoresponsive property was also observed in Ch-HPC Nanogel-cross-linked macrogels. These results suggest that a Ch-HPC Nanogel is an attractive building block for thermoresponsive Nanogel tectonic materials.
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Current advances in self-assembled Nanogel delivery systems for immunotherapy
Advanced drug delivery reviews, 2015Co-Authors: Yoshiro Tahara, Kazunari AkiyoshiAbstract:Since Nanogels (nanometer-sized gels) were developed two decades ago, they were utilized as carriers of innovative drug delivery systems. In particular, immunological drug delivery via self-assembled Nanogels (self-Nanogels) owing to their nanometer size and molecular chaperon-like ability to encapsulate large biomolecules is one of the most well studied and successful applications of Nanogels. In the present review, we focus on self-Nanogel applications as immunological drug delivery systems for cancer vaccines, cytokine delivery, nasal vaccines, and nucleic acid delivery, including several clinical trials. Cancer vaccines were the first practical application of self-Nanogels as vehicles for drug delivery. After successful pre-clinical studies, phase I clinical trials were conducted, and it was found that vaccines consisting of self-Nanogels could be administered repeatedly to humans without serious adverse effects, and self-Nanogel vaccines induced antigen-specific cellular and humoral immunity. Cytokine delivery via self-Nanogels led to the sustained release of IL-12, suppressed tumor growth, and increased Th1-type immune responses. Cationic self-Nanogels were effective in penetrating the nasal mucosa and resulted in successful nasal vaccines in mice and nonhuman primates. Cationic self-Nanogels were also used for the intracellular delivery of proteins and nucleic acids, and were successfully used to knockdown tumor growth factor expression using short interfering RNA with the immunological effect. These studies suggest that self-Nanogels are currently one of the most unique and attractive immunological drug delivery systems and are edging closer to practical use.
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Nanogel tectonic porous gel loading biologics nanocarriers and cells for advanced scaffold
Biomaterials, 2015Co-Authors: Yoshihide Hashimoto, Sadaatsu Mukai, Yoshihiro Sasaki, Shinichi Sawada, Kazunari AkiyoshiAbstract:Abstract 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 ( G ′) 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.
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Nanogel bottom up gel biomaterials for protein delivery photopolymerization of an acryloyl modified polysaccharide Nanogel macromonomer
Reactive & Functional Polymers, 2013Co-Authors: Yoshiro Tahara, Yoshihiro Sasaki, Shinichi Sawada, Satoshi Kosuge, Kazunari AkiyoshiAbstract:Abstract Polysaccharide Nanogels are one of the most attractive carriers for drug delivery systems. Nanogels encapsulate proteins in their hydrated polymer networks, and minimize the denaturation of proteins. In this study, we demonstrated the cross-linking of acryloyl group-modified polysaccharide Nanogels via photopolymerization, which allowed the formation of novel hydrogel particles and macrogels. The mechanical properties of the resultant hydrogels depended on the concentrations of the Nanogels and the cross-linkers. The most significant property of the Nanogel-cross-linked hydrogel was the ability to encapsulate insulin via hydrophobic interactions. After incubation of the hydrogel containing insulin in water, the hydrogel was degraded by hydrolysis, and insulin was gradually released from the hydrogels over a period of 1 week. According to these results, this Nanogel-cross-linked hydrogel prepared via photopolymerization has potential for innovative biomaterials.
Serguei V Vinogradov - One of the best experts on this subject based on the ideXlab platform.
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hyaluronic acid based Nanogel drug conjugates with enhanced anticancer activity designed for the targeting of cd44 positive and drug resistant tumors
Bioconjugate Chemistry, 2013Co-Authors: Xin Wei, Thulani H Senanayake, Galya Warren, Serguei V VinogradovAbstract:Many drug-resistant tumors and cancer stem cells (CSC) express elevated levels of CD44 receptor, a cellular glycoprotein binding hyaluronic acid (HA). Here, we report the synthesis of Nanogel-drug conjugates based on membranotropic cholesteryl-HA (CHA) for efficient targeting and suppression of drug-resistant tumors. These conjugates significantly increased the bioavailability of poorly soluble drugs with previously reported activity against CSC, such as etoposide, salinomycin, and curcumin. The small Nanogel particles (diameter 20-40 nm) with a hydrophobic core and high drug loads (up to 20%) formed after ultrasonication and demonstrated a sustained drug release following the hydrolysis of biodegradable ester linkage. Importantly, CHA-drug Nanogels demonstrated 2-7 times higher cytotoxicity in CD44-expressing drug-resistant human breast and pancreatic adenocarcinoma cells compared to that of free drugs and nonmodified HA-drug conjugates. These Nanogels were efficiently internalized via CD44 receptor-mediated endocytosis and simultaneous interaction with the cancer cell membrane. Anchoring by cholesterol moieties in the cellular membrane after Nanogel unfolding evidently caused more efficient drug accumulation in cancer cells compared to that in nonmodified HA-drug conjugates. CHA-drug Nanogels were able to penetrate multicellular cancer spheroids and displayed a higher cytotoxic effect in the system modeling tumor environment than both free drugs and HA-drug conjugates. In conclusion, the proposed design of Nanogel-drug conjugates allowed us to significantly enhance drug bioavailability, cancer cell targeting, and the treatment efficacy against drug-resistant cancer cells and multicellular spheroids.
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hyaluronic acid based Nanogel drug conjugates with enhanced anticancer activity designed for the targeting of cd44 positive and drug resistant tumors
Bioconjugate Chemistry, 2013Co-Authors: Xin Wei, Thulani H Senanayake, Galya Warren, Serguei V VinogradovAbstract:Many drug-resistant tumors and cancer stem cells (CSC) express elevated levels of CD44 receptor, a cellular glycoprotein binding hyaluronic acid (HA). Here, we report the synthesis of Nanogel–drug conjugates based on membranotropic cholesteryl-HA (CHA) for efficient targeting and suppression of drug-resistant tumors. These conjugates significantly increased the bioavailability of poorly soluble drugs with previously reported activity against CSC, such as etoposide, salinomycin, and curcumin. The small Nanogel particles (diameter 20–40 nm) with a hydrophobic core and high drug loads (up to 20%) formed after ultrasonication and demonstrated a sustained drug release following the hydrolysis of biodegradable ester linkage. Importantly, CHA–drug Nanogels demonstrated 2–7 times higher cytotoxicity in CD44-expressing drug-resistant human breast and pancreatic adenocarcinoma cells compared to that of free drugs and nonmodified HA–drug conjugates. These Nanogels were efficiently internalized via CD44 receptor-medi...
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polymeric Nanogels containing the triphosphate form of cytotoxic nucleoside analogues show antitumor activity against breast and colorectal cancer cell lines
Molecular Cancer Therapeutics, 2008Co-Authors: Carlos M Galmarini, Ekta Kohli, Arin D Zeman, Galya Warren, Anton Mitin, Serguei V VinogradovAbstract:The therapeutic efficiency of anticancer nucleoside analogues (NA) strongly depends on their intracellular accumulation and conversion into 5′-triphosphates. Because active NATP cannot be directly administrated due to instability, we present here a strategy of nanoencapsulation of these active drugs for efficient delivery to tumors. Stable lyophilized formulations of 5′-triphosphates of cytarabine (araCTP), gemcitabine (dFdCTP), and floxuridine (FdUTP) encapsulated in biodegradable PEG- cl -PEI or F127- cl -PEI Nanogel networks (NGC and NGM, respectively) were prepared by a self-assembly procedure. Cellular penetration, in vitro cytotoxicity, and drug-induced cell cycle perturbations of these nanoformulations were analyzed in breast and colorectal cancer cell lines. Cellular accumulation and NATP release from Nanogel was studied by confocal microscopy and direct high-performance liquid chromatography analysis of cellular lysates. Antiproliferative effect of dFdCTP nanoformulations was evaluated in human breast carcinoma MCF7 xenograft animal model. Nanoencapsulated araCTP, dFdCTP, and FdUTP showed similar to NA cytotoxicity and cell cycle perturbations. Nanogels without drugs showed very low cytotoxicity, although NGM was more toxic than NGC. Treatment by NATP nanoformulations induced fast increase of free intracellular drug concentration. In human breast carcinoma MCF7 xenograft animal model, i.v. dFdCTP-Nanogel was equally effective in inhibiting tumor growth at four times lower administered drug dose compared with free gemcitabine. Active triphosphates of NA encapsulated in Nanogels exhibit similar cytotoxicity and cell cycle perturbations in vitro and faster cell accumulation and equal tumor growth-inhibitory activity in vivo at much lower dose compared with parental drugs, illustrating their therapeutic potential for cancer chemotherapy. [Mol Cancer Ther 2008;7(10):3373–80]
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formulations of biodegradable Nanogel carriers with 5 triphosphates of nucleoside analogs that display a reduced cytotoxicity and enhanced drug activity
Journal of Controlled Release, 2007Co-Authors: Ekta Kohli, Huai Yun Han, Arin D Zeman, Serguei V VinogradovAbstract:Therapies including nucleoside analogs are associated with severe toxic side effects and acquirement of drug resistance. We have previously reported the drug delivery in the form of 5′-triphosphates (NTP) encapsulated in cross-linked cationic networks of polyethylenimine (PEI) and PEG/Pluronic® polymers (Nanogels). In this study, Nanogels, containing biodegradable PEI that could easily dissociate in reducing cytosolic environment and form products with minimal toxicity, were synthesized and displayed low cytotoxicity. Toxicity of Nanogels was clearly dependent on the total positive charge of carriers and was 5–6-fold lower for carriers loaded with NTP. Though intracellular ATP level was immediately reduced by ca. 50% following the treatment with Nanogels, it was largely restored 24 h later. Effect of Nanogels on various respiratory components of cells was reversible too, and, therefore, resulted in low immediate cell death. Nanogel alone and formulations with AZT-TP demonstrated a much lower mitochondrial toxicity than AZT. As an example of potential antiviral applications of low-toxic Nanogel carriers, a 5′-triphosphorylated Ribavirin-Nanogel formulation was prepared that demonstrated a 30-fold decrease in effective drug concentration (EC90) and, totally, a 10-fold increase in selectivity index compared to the drug alone in MDCK cells infected with influenza A virus.
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polyplex Nanogel formulations for drug delivery of cytotoxic nucleoside analogs
Journal of Controlled Release, 2005Co-Authors: Serguei V Vinogradov, Arin D Zeman, Elena V Batrakova, Alexander V KabanovAbstract:Hydrophilic nanosized particles consisting of the cross-linked cationic polymer network (Nanogels) are suggested as a drug delivery system for nucleoside analog 5'-triphosphates, an active form of cytotoxic anticancer drugs. Preparation, properties, and cellular effects of several polyplex Nanogel formulations with the 5'-triphosphate of cytotoxic 5-fluoroadenine arabinoside (fludarabine) (FATP) were examined and discussed here. The polyplexes have formed spontaneously by mixing solutions of FATP and Nanogels because of ionic interactions between protonated polyethylenimine (PEI) chains in Nanogel network with polyphosphate groups of the drug. Subsequent compaction of the flexible Nanogel network has resulted in an encapsulation of the FATP/PEI complex in a dense core surrounded by hydrophilic poly(ethylene glycol) (PEG) envelope. This structure has provided a sustained release of the drug, as well as an efficient protection of FATP against enzymatic degradation. The drug loading could reach up to 33% by weight of the drug-Nanogel formulation. In vitro 35% of loaded drug has released from Nanogel formulations during the first 24 h, and a slower additional release was observed during the next 2 days. Nanogels have protected 90% of the encapsulated FATP from enzymatic dephosphorylation during the first 60 min of incubation in vitro. The drug-Nanogel formulation compared to the drug has demonstrated a significantly enhanced cytotoxicity in cultured cancer cells. Cancer cell-targeting molecules, such as folate, could be easily attached to Nanogels and this modification has resulted in a strong 10-fold increase of the carrier's internalization in human breast carcinoma MCF-7 cells. Moreover, transcellular transport of the folate-Nanogel polyplexes was found to be 4 times more effective compared to the drug alone using Caco-2 cell monolayers as an in vitro intestinal model. The data demonstrate that this carrier-based approach to delivery of cytotoxic drugs may enhance tumor specificity and significantly reduce side effects related to systemic toxicity usually observed during cancer chemotherapy.
Yoshihiro Sasaki - One of the best experts on this subject based on the ideXlab platform.
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Nanogel integrated ph responsive composite hydrogels for controlled drug delivery
ACS Biomaterials Science & Engineering, 2017Co-Authors: Gunce E Cinay, Kazunari Akiyoshi, Yoshihiro Sasaki, Pelin Erkoc, Mohammad Alipour, Yoshihide Hashimoto, Seda KizilelAbstract:A novel pH-sensitive hydrogel system consisting of poly(methacrylic acid-g-ethylene glycol) (P(MAA-g-EG)) and acryloyl group modified-cholesterol-bearing pullulan (CHPOA) Nanogels was developed for the controlled delivery of an anticonvulsant drug, pregabalin (PGB). Here, the hydrophilic hydrogel network provides the pH-sensitive swelling behavior, whereas Nanogel components form separate reservoirs for the delivery of drugs with different hydrophobicities. These nanocarrier-integrated hybrid gels were synthesized through both surface-initiated and bulk photopolymerization approaches. The swelling and drug release behavior of these pH-responsive hydrogels synthesized by different photopolymerization approaches at visible and UV light wavelenghts were studied at acidic and basic pH values. Nanogel-integrated hydrogels exhibited higher swelling behavior compared to plain hydrogels in reversible swelling experiments. Similarly, the presence of Nanogels in hydrogel network enhanced the loading and release per...
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self assembled Nanogels of cholesterol bearing hydroxypropyl cellulose a thermoresponsive building block for Nanogel tectonic materials
Langmuir, 2016Co-Authors: Yoshiro Tahara, Yoshihiro Sasaki, Mizuki Sakiyama, Shigeo Takeda, Tomoki Nishimura, Sadaatsu Mukai, Shinichi Sawada, Kazunari AkiyoshiAbstract:Hydroxypropyl cellulose (HPC) is a fascinating polysaccharide to use in developing a Nanogel to be a thermoresponsive building unit for Nanogel tectonic materials. Cholesterol-bearing HPC (Ch-HPC) self-assembled to form Nanogels through hydrophobic interactions of the cholesteryl groups in water. Ch-HPC Nanogels had a lower critical solution temperature in line with that of native HPC. The particle size of Ch-HPC Nanogels was reversibly controlled by the temperature and salting-out effect. The thermoresponsive property was also observed in Ch-HPC Nanogel-cross-linked macrogels. These results suggest that a Ch-HPC Nanogel is an attractive building block for thermoresponsive Nanogel tectonic materials.
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Nanogel tectonic porous gel loading biologics nanocarriers and cells for advanced scaffold
Biomaterials, 2015Co-Authors: Yoshihide Hashimoto, Sadaatsu Mukai, Yoshihiro Sasaki, Shinichi Sawada, Kazunari AkiyoshiAbstract:Abstract 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 ( G ′) 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.
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Nanogel bottom up gel biomaterials for protein delivery photopolymerization of an acryloyl modified polysaccharide Nanogel macromonomer
Reactive & Functional Polymers, 2013Co-Authors: Yoshiro Tahara, Yoshihiro Sasaki, Shinichi Sawada, Satoshi Kosuge, Kazunari AkiyoshiAbstract:Abstract Polysaccharide Nanogels are one of the most attractive carriers for drug delivery systems. Nanogels encapsulate proteins in their hydrated polymer networks, and minimize the denaturation of proteins. In this study, we demonstrated the cross-linking of acryloyl group-modified polysaccharide Nanogels via photopolymerization, which allowed the formation of novel hydrogel particles and macrogels. The mechanical properties of the resultant hydrogels depended on the concentrations of the Nanogels and the cross-linkers. The most significant property of the Nanogel-cross-linked hydrogel was the ability to encapsulate insulin via hydrophobic interactions. After incubation of the hydrogel containing insulin in water, the hydrogel was degraded by hydrolysis, and insulin was gradually released from the hydrogels over a period of 1 week. According to these results, this Nanogel-cross-linked hydrogel prepared via photopolymerization has potential for innovative biomaterials.
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Nanogel engineering for new nanobiomaterials from chaperoning engineering to biomedical applications
Chemical Record, 2010Co-Authors: Yoshihiro Sasaki, Kazunari AkiyoshiAbstract:Nanosize hydrogels (Nanogels) are polymer nanoparticles with three-dimensional networks, formed by chemical and/or physical cross-linking of polymer chains. Recently, various Nanogels have been designed, with a particular focus on biomedical applications. In this review, we describe recent progress in the synthesis of Nanogels and Nanogel-integrated hydrogels (Nanogel cross-linked gels) for drug-delivery systems (DDS), regenerative medicine, and bioimaging. We also discuss chaperone-like functions of physical cross-linking Nanogel (chaperoning engineering) and organic-inorganic hybrid Nanogels.
Shuiqin Zhou - One of the best experts on this subject based on the ideXlab platform.
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chitosan based responsive hybrid Nanogels for integration of optical ph sensing tumor cell imaging and controlled drug delivery
Biomaterials, 2010Co-Authors: Weitai Wu, Probal Banerjee, Jing Shen, Shuiqin ZhouAbstract:We report a new class of chitosan-based hybrid Nanogels by in-situ immobilization of CdSe quantum dots (QDs) in the chitosan-poly(methacrylic acid) (chitosan-PMAA) networks. The covalently crosslinked hybrid Nanogels with chitosan chains semi-interpenetrating in the crosslinked PMAA networks exhibit excellent colloidal and structural stability as well as reversible physical property change in response to a pH variation cross the physiological condition. In contrast, the hybrid Nanogels formed by non-covalent physical association exhibit a significant change in the structure and composition upon exposure to physiological pH. This distinction in the structural stability of hybrid Nanogels produces very different outcomes for their biomedical applications. The covalently crosslinked hybrid Nanogels are low-cytotoxic and could illuminate the B16F10 cells, sense the environmental pH change, and regulate the release of anticancer drug in the typical abnormal pH range of 5-7.4 found in pathological zone, thus successfully combine multiple functionality into a single nano-object. However, the physically associated hybrid Nanogels exhibit a non-reversible pH-sensitive PL property and a significant cytotoxicity after 24 h treatment. It is critical to construct a highly stable biopolymer-QD hybrid Nanogel, via a rational design for safe bionanomaterials, to simultaneously combine the biosensing, bioimaging, and effective therapy functions.
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smart core shell hybrid Nanogels with ag nanoparticle core for cancer cell imaging and gel shell for ph regulated drug delivery
Chemistry of Materials, 2010Co-Authors: Weitai Wu, Ting Zhou, Alexandra Berliner, Probal Banerjee, Shuiqin ZhouAbstract:Multifunctional nanoparticles that can provide long circulation and specific accumulation, illuminate the targeted object, and intelligently dose the pathological zones will enable major advancements in diagnosis and therapy. To facilitate a simultaneous tumor-cell imaging and adequate local delivery to the tumor site, we develop core−shell structured hybrid Nanogels (40−80 nm) composed of a Ag nanoparticle (NP) as core and smart gel of poly(N-isopropylacrylamide-co-acrylic acid) as shell. The pH-induced shrinkage of the Nanogel increases the UV−vis absorption intensity and causes a blue shift of the surface plasmon bands of the Ag NP core. The smart Nanogel can overcome cellular barriers to enter the intracellular region and light up the mouse melanoma B16F10 cells, including the nuclear regions. The surface property and concentrations of the hybrid Nanogels influences their interactions with cells, resulting in different cell morphology and selective cell staining. The pH-responsive hybrid Nanogels exhi...
Shinichi Sawada - One of the best experts on this subject based on the ideXlab platform.
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self assembled Nanogels of cholesterol bearing hydroxypropyl cellulose a thermoresponsive building block for Nanogel tectonic materials
Langmuir, 2016Co-Authors: Yoshiro Tahara, Yoshihiro Sasaki, Mizuki Sakiyama, Shigeo Takeda, Tomoki Nishimura, Sadaatsu Mukai, Shinichi Sawada, Kazunari AkiyoshiAbstract:Hydroxypropyl cellulose (HPC) is a fascinating polysaccharide to use in developing a Nanogel to be a thermoresponsive building unit for Nanogel tectonic materials. Cholesterol-bearing HPC (Ch-HPC) self-assembled to form Nanogels through hydrophobic interactions of the cholesteryl groups in water. Ch-HPC Nanogels had a lower critical solution temperature in line with that of native HPC. The particle size of Ch-HPC Nanogels was reversibly controlled by the temperature and salting-out effect. The thermoresponsive property was also observed in Ch-HPC Nanogel-cross-linked macrogels. These results suggest that a Ch-HPC Nanogel is an attractive building block for thermoresponsive Nanogel tectonic materials.
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Nanogel tectonic porous gel loading biologics nanocarriers and cells for advanced scaffold
Biomaterials, 2015Co-Authors: Yoshihide Hashimoto, Sadaatsu Mukai, Yoshihiro Sasaki, Shinichi Sawada, Kazunari AkiyoshiAbstract:Abstract 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 ( G ′) 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.
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Nanogel bottom up gel biomaterials for protein delivery photopolymerization of an acryloyl modified polysaccharide Nanogel macromonomer
Reactive & Functional Polymers, 2013Co-Authors: Yoshiro Tahara, Yoshihiro Sasaki, Shinichi Sawada, Satoshi Kosuge, Kazunari AkiyoshiAbstract:Abstract Polysaccharide Nanogels are one of the most attractive carriers for drug delivery systems. Nanogels encapsulate proteins in their hydrated polymer networks, and minimize the denaturation of proteins. In this study, we demonstrated the cross-linking of acryloyl group-modified polysaccharide Nanogels via photopolymerization, which allowed the formation of novel hydrogel particles and macrogels. The mechanical properties of the resultant hydrogels depended on the concentrations of the Nanogels and the cross-linkers. The most significant property of the Nanogel-cross-linked hydrogel was the ability to encapsulate insulin via hydrophobic interactions. After incubation of the hydrogel containing insulin in water, the hydrogel was degraded by hydrolysis, and insulin was gradually released from the hydrogels over a period of 1 week. According to these results, this Nanogel-cross-linked hydrogel prepared via photopolymerization has potential for innovative biomaterials.
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amphiphilic polysaccharide nanoballs a new building block for Nanogel biomedical engineering and artificial chaperones
ACS Nano, 2011Co-Authors: Haruko Takahashi, Shinichi Sawada, Kazunari AkiyoshiAbstract:Enzymatically synthesized glycogen (ESG), a highly branched (1→4)(1→6)-linked α-glucan, is a new monodisperse spherical hyperbranched nanoparticle (molecular weight, 106−107; diameter, 20−30 nm), polysaccharide nanoball. Amphiphilic ESG nanoballs were synthesized by introducing a cholesterol group to enzymatically synthesized glycogen (CHESG). CHESG assembled into a structure containing a few molecules to form cluster Nanogels (approximately 35 nm in diameter) in water. The cluster Nanogels were dissociated by the addition of cyclodextrin (CD) to form a supramolecular CHESG−CD nanocomplex due to complexation with the cholesterol group and CD. The CHESG Nanogel showed high capacity for complexation with proteins, and the CHESG−CD nanocomplex showed high chaperone-like activity for thermal stabilization of enzymes. CHESG has great potential to become a new building block for Nanogel biomedical engineering and to act as an artificial chaperone for protein engineering.
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nano encapsulation of lipase by self assembled Nanogels induction of high enzyme activity and thermal stabilization
Macromolecular Bioscience, 2010Co-Authors: Shinichi Sawada, Kazunari AkiyoshiAbstract:The effects of self-assembled polysaccharide Nanogels on colloidal and thermal stability of lipase from Pseudomonas cepacia were investigated. The enzyme activity, especially k(cat), drastically increased in the presence of Nanogels of cholesterol-bearing pullulan (CHP). The thermostability of lipase complex increased because the denaturation temperature of lipase increased by more than 20 degrees C by complexation with CHP Nanogels. Lipase denaturation and aggregation upon heating was effectively prevented by complexation with CHP Nanogels. Moreover, complexation with CHP Nanogels protected lipase from lyophilization-induced aggregation. Nano-encapsulation with CHP Nanogel is a useful method for colloidal and thermal stabilization of unstable enzyme.
