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Kazunori Kataoka - One of the best experts on this subject based on the ideXlab platform.
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Manipulating dynamic tumor vessel permeability to enhance Polymeric Micelle accumulation.
Journal of controlled release : official journal of the Controlled Release Society, 2020Co-Authors: Yuta Inoue, Kazunori Kataoka, Yu Matsumoto, Kazuko Toh, Kazuki Miyano, Horacio Cabral, Kazunori Igarashi, Shinichi Iwasaki, Tatsuya YamasobaAbstract:Selectively delivering anticancer drugs to solid tumors while avoiding their accumulation in healthy tissues is a major goal in Polymeric Micelle research. We have recently discovered that the extravasation and permeation of Polymeric Micelles occur in a dynamic manner characterized by vascular bursts followed by a brief and vigorous outward flow of fluid (called "nano-eruptions"). Nano-eruptions allow delivery of Polymeric Micelle-associated drugs, though delivery can be heterogeneous both among tumors and within an individual tumor, leading to suboptimal intratumoral distribution. Manipulation of nano-eruptions is expected to improve the efficiency of drug delivery systems (DDSs). By using compounds that affect the intratumoral environment, i.e. a TGF-β inhibitor and chloroquine, the possibility of manipulating nano-eruptions to improve delivery efficiency was investigated. Both compounds were tested in a mouse xenograft model of GFP-labeled pancreatic tumor cells by tracing nano-eruption events and extravasation of size-modulated Polymeric Micelles in real-time through intravital confocal laser scanning microscopy. The TGF-β inhibitor increased the number of dynamic vents, extended duration time, and generated dynamic vents with a wide range of sizes. Chloroquine did not affect the frequency of nano-eruptions, but it increased tumor vessel diameter, maximum nano-eruption area, and maximum radial increase. Both the TGF-β inhibitor and chloroquine augmented nano-eruptions to diffuse Polymeric Micelles through tumor stroma, and these medications had a greater effect on the Polymeric Micelles with larger size, i.e. 70-nm, than on the smaller Polymeric Micelles having a 30-nm diameter. The results indicate that TGF-β inhibition and chloroquine refashion the intratumoral distribution of DDSs by different mechanisms.
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controlled fab installation onto Polymeric Micelle nanoparticles for tuned bioactivity
Science and Technology of Advanced Materials, 2017Co-Authors: Shaoyi Chen, Kazunori Kataoka, Horacio Cabral, Stelios Florinas, Abigail Teitgen, Changshou Gao, James R ChristieAbstract:AbstractAntibodies and antigen-binding fragments (Fabs) can be used to modify the surface of nanoparticles for enhanced target binding. In our previous work, site-specific conjugation of Fabs to Polymeric Micelles using conventional methods was limited to approximately 30% efficiency, possibly due to steric hindrance related to macromolecular reactants. Here, we report a new method that enables conjugation of Fabs onto a Micelle surface in a controlled manner with up to quantitative conversion of nanoparticle reactive groups. Variation of (i) PEG spacer length in a heterofunctionalized cross-linker and (ii) Fab/polymer feed ratios resulted in production of nanoparticles with a range of Fab densities on the surface up to the theoretical maximum value. The biological impact of variable Fab density was evaluated in vitro with respect to cell uptake and cytotoxicity of a drug-loaded (SN38) targeted Polymeric Micelle bearing anti-EphA2 Fabs. Fab conjugation increased cell uptake and potency compared with non-t...
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three layered polyplex Micelle as a multifunctional nanocarrier platform for light induced systemic gene transfer
Nature Communications, 2014Co-Authors: Takahiro Nomoto, Nobuhiro Nishiyama, Kensuke Osada, Yu Matsumoto, Shigeto Fukushima, Michiaki Kumagai, Kaori Machitani, Kanjiro Miyata, Kazunori KataokaAbstract:Light-controlled mechanisms for the delivery of drug molecules to cells is a promising route for non-invasive disease therapy. Here, the authors develop a photosensitive Polymeric Micelle for light-induced gene transfection and show its effectiveness in vivo via systemic administration.
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dendrimer phthalocyanine encapsulated Polymeric Micelle mediated photochemical internalization extends the efficacy of photodynamic therapy and overcomes drug resistance in vivo
Journal of Controlled Release, 2011Co-Authors: Wei Jhe Syu, Kazunori Kataoka, Nobuhoro Nishiyama, Pingshan LaiAbstract:Clinically, the efficacy of chemotherapeutic agents can be dramatically reduced in cancer cells with multiple drug resistance (MDR). In doxorubicin-resistant breast cancer cells, drugs accumulate only within discrete cytosolic organelles that abrogate their therapeutic effects in vitro and in vivo. Photochemical internalization (PCI), a specific branch of photodynamic therapy (PDT), is a novel strategy utilized for the site-specific triggered drug/gene release. The objective of this study was to evaluate the nanoparticle-based PDT/PCI effects on the reversal of drug resistance. Dendrimer phthalocyanine-encapsulated Polymeric Micelle (DPc/m)-mediated PCI, combined with doxorubicin, was studied in drug-resistant MCF-7 cells and a xenograft model. Our results show that the internalized DPc/m showed unique PCI properties inside the cells and thereby facilitating doxorubicin release from the endo-lysosomes to nuclei after photoirradiation. Moreover, ‘light before’ PCI showed the highest antitumor efficacy and the depth of the proliferating cell nuclear antigen-negative area in tumor sections after DPc/m-mediated PDT was obviously increased by combination therapy with doxorubicin; this indicates the limitation of depth of light penetration in PDT, which may be improved by PCI. We conclude that nanotechnology-based PCI possesses several clinical benefits, such as overcoming drug resistance and treating deeper lesions that are intractable by PDT alone.
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in vivo antitumor activity of the folate conjugated ph sensitive Polymeric Micelle selectively releasing adriamycin in the intracellular acidic compartments
Bioconjugate Chemistry, 2007Co-Authors: Nobuhiro Nishiyama, Kazunori KataokaAbstract:Cancer treatment efficacy and safety of the environmentally sensitive Polymeric Micelle drug carriers were significantly increased by optimizing the number of ligands on their surface. These Micelles were designed to target the cancerous tumors through the interaction between folate and its receptors that overexpress on the cancer cell membrane while achieving pH-controlled drug release in the intracellular acidic compartments such as endosomes and lysosomes. In order to elucidate the effects of folate on cytotoxicity, biodistribution, anticancer activity, and pharmacological properties, folate concentration on the surface of the Micelles was controlled by precise synthesis of two different amphiphilic block copolymers that self-assemble into spherical Micelles, folate−poly(ethylene glycol)−poly(aspartate-hydrazone-adriamycin) with γ-carboxylic acid activated folate and methoxy-poly(ethylene glycol)−poly(aspartate-hydrazone-adriamycin) without folate. It is of significance that, although folate conjugatio...
Masayuki Yokoyama - One of the best experts on this subject based on the ideXlab platform.
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Toxicity and immunogenicity concerns related to PEGylated-Micelle carrier systems: a review
Taylor & Francis Group, 2019Co-Authors: Kouichi Shiraishi, Masayuki YokoyamaAbstract:Polymeric-Micelle carrier systems have emerged as a novel drug-carrier system and have been actively studied for anticancer drug targeting. In contrast, toxicological and immunological concerns related to not only Polymeric-Micelle carrier systems, but also other nanocarrier systems, have received little attention owing to researchers’ focus on therapeutic effects. However, in recent clinical contexts, biopharmaceuticals’ effects on immune responses have come to light, requiring that researchers substantively explore the potential negative side effects of nanocarrier systems and of therapeutic proteins in order to develop nanocarrier systems suitable for clinical use. The present review describes current insights into both toxicological and immunological issues regarding Polymeric-Micelle carrier systems. The review focuses on immunogenicity issues of Polymeric-Micelle carrier systems possessing poly(ethylene glycol) (PEG). We conclude that PEG-related immunogenicity is deeply related to characteristics of a counterpart block of PEG-conjugates, and we propose future directions for addressing this unresolved issue
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peg poly l lysine based Polymeric Micelle mri contrast agent feasibility study of a gd Micelle contrast agent for mr lymphography
Journal of Magnetic Resonance Imaging, 2018Co-Authors: Hiroyuki Akai, Masayuki Yokoyama, Kouichi Shiraishi, Koichiro Yasaka, Masanori Nojima, Yusuke Inoue, Osamu Abe, Kuni Ohtomo, Shigeru KiryuAbstract:PURPOSE To investigate the feasibility of Polymeric Micelle of poly(ethyleneglycol) (PEG)-b-poly(L-lysine-DOTA) (Gd-Micelle) as a contrast agent for magnetic resonance lymphography (MRL). MATERIALS AND METHODS Twenty-four female BALB/c mice were randomly divided into four groups of six mice each. Among them, mice of two groups were injected of complete Freund's adjuvant to obtain inflamed lymph nodes. We subcutaneously injected 0.5 μmol Gd per mouse of Gd-Micelle or gadofluorine P in the right rear footpad. Identical 3D T1 -weighted gradient-echo imaging (1T MRI system) were subsequently obtained to create time-intensity curves of the right popliteal, sacral, and lumbar-aortic lymph nodes and to measure the contrast ratios (CRs). The peak CR, area under the curve (AUC), and elimination half-life (T1/2 ) of CR of the popliteal lymph node were assessed by two-way factorial analysis of variance. We also performed a qualitative assessment of normal and inflamed lymph node at three timepoints. RESULTS The mean peak CR of Gd-Micelle was 2.64 and 1.89 for gadofluorine P in normal mice, and 3.48 and 2.73 in the inflamed lymph node. Statistically, peak CR was higher for Gd-Micelle (P = 0.004). In addition, the AUC was larger (P < 0.001) and T1/2 was longer (P < 0.001) for Gd-Micelle. In qualitative assessment, Gd-Micelle demonstrated the same or higher scores in every lymph node, and demonstrated a higher score in lumbar-aortic lymph node of a 360-minute image (P = 0.006) and in inflamed lymph node of a 360-minute image (P = 0.009). CONCLUSION Compared to gadofluorine P, Gd-Micelle showed higher and more prolonged enhancement in MRL imaging in normal and inflamed lymph nodes. LEVEL OF EVIDENCE 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:238-245.
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a Polymeric Micelle magnetic resonance imaging mri contrast agent reveals blood brain barrier bbb permeability for macromolecules in cerebral ischemia reperfusion injury
Journal of Controlled Release, 2017Co-Authors: Kouichi Shiraishi, Zuojun Wang, Daisuke Kokuryo, Ichio Aoki, Masayuki YokoyamaAbstract:Abstract Blood–brain barrier (BBB) opening is a key phenomenon for understanding ischemia-reperfusion injuries that are directly linked to hemorrhagic transformation. The recombinant human tissue-type plasminogen activator (rtPA) increases the risk of symptomatic intracranial hemorrhages. Recent imaging technologies have advanced our understanding of pathological BBB disorders; however, an ongoing challenge in the pre-“rtPA treatment” stage is the task of developing a rigorous method for hemorrhage-risk assessments. Therefore, we examined a novel method for assessment of rtPA-extravasation through a hyper-permeable BBB. To examine the image diagnosis of rtPA-extravasation for a rat transient occlusion-reperfusion model, in this study we used a Polymeric Micelle MRI contrast-agent (Gd-Micelles). Specifically, we used two MRI contrast agents at 1 h after reperfusion. Gd-Micelles provided very clear contrast images in 15.5 ± 10.3% of the ischemic hemisphere at 30 min after i.v. injection, whereas a classic gadolinium chelate MRI contrast agent provided no satisfactorily clear images. The obtained images indicate both the hyper-permeable BBB area for macromolecules and the distribution area of macromolecules in the ischemic hemisphere. Owing to their large molecular weight, Gd-Micelles remained in the ischemic hemisphere through the hyper-permeable BBB. Our results indicate the feasibility of a novel clinical diagnosis for evaluating rtPA-related hemorrhage risks.
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Polymeric Micelles as drug carriers: their lights and shadows.
Journal of drug targeting, 2014Co-Authors: Masayuki YokoyamaAbstract:In this review, Polymeric Micelles as drug-targeting carriers are concisely explained. In the first introduction part, I describe a brief history of polymer Micelle's research for drug targeting, and then I explain this review's focus. Since most other review articles concerning Polymeric Micelle carriers explain only what was achieved in the Polymeric Micelle's research, I describe this review by focusing on what was not done. In the second part, I take up three characteristics of Polymeric Micelle carriers by comparing their advantages and disadvantages, what was done and what was not done in the past studies, and what is easily achieved and what is difficult to be achieved with Polymeric Micelles. In the last part, I discuss three common problems of nano-sized drug carrier systems including Polymeric Micelles, and then I add a few comments on these problems.
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clinical applications of Polymeric Micelle carrier systems in chemotherapy and image diagnosis of solid tumors
Journal of Experimental & Clinical Medicine, 2011Co-Authors: Masayuki YokoyamaAbstract:Polymeric Micelles are assemblies of synthetic polymers and have been studied and developed as drug carriers for targeting solid tumors. Physicochemical characters and medical advantages of the Polymeric Micelle carrier systems are summarized, followed by an explanation of their recent application for contrast agent targeting. In the final section, future perspectives on the Polymeric Micelle carrier systems for tumor targeting are discussed, including a novel combination of contrast agent targeting and drug targeting that achieves tumor-specific image diagnosis and tumor-selective chemotherapy, respectively.
Yusuke Yamauchi - One of the best experts on this subject based on the ideXlab platform.
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pore tuning to boost the electrocatalytic activity of Polymeric Micelle templated mesoporous pd nanoparticles
Chemical Science, 2019Co-Authors: Muhammad Iqbal, Bo Jiang, Zhongli Wang, Jeonghun Kim, Ashok Kumar Nanjundan, Andrew E Whitten, Kathleen Wood, Yusuke YamauchiAbstract:Understanding how mesoporous noble metal architectures affect electrocatalytic performance is very important for the rational design and preparation of high-performance electrocatalysts. Herein, by using Polymeric Micelle-assembled structures as templates, mesoporous Pd nanoparticles with tunable porous constructions are synthesized by simply tuning the solvent compositions. The effect of porous Pd nanoparticles on the electrocatalytic performance is thoroughly studied. Their superior electrocatalytic activity can be attributed to the mass transport efficiency and open porous structures.
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Synthesis of Mesoporous Transition-Metal Phosphates by Polymeric Micelle Assembly.
Chemistry (Weinheim an der Bergstrasse Germany), 2016Co-Authors: Bishnu Prasad Bastakoti, Zongwen Liu, Sudhina Guragain, Malay Pramanik, Saad M. Alshehri, Tansir Ahamad, Yusuke YamauchiAbstract:Mesoporous iron phosphate (FePO4) was synthesized through assembly of Polymeric Micelles made of asymmetric triblock co-polymer (polystyrene-b-poly-2-vinylpyridine-b-ethylene oxide; PS-PVP-PEO). The phosphoric acid solution stimulates the formation of Micelles with core-shellcorona architecture. The negatively charged PO43- ions dissolved in the solution strongly interact with the positively charged PVP+ units through an electrostatic attraction. Also, the presence of PO43- ions realizes a bridge between the mi-celle surface and the metal ions. The removal of Polymeric template forms the robust framework of iron phosphate with 30 nm pore diameter and 15 nm wall thickness. Our method is applicable to other mesoporous metal phosphates by changing metal sources. The obtained materials were fully characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), N-2 adsorption- desorption, Raman spectroscope, and other techniques.
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mesoporous tio2 zn2ti3o8 hybrid films synthesized by Polymeric Micelle assembly
Chemical Communications, 2015Co-Authors: Ming Zhao, Bishnu Prasad Bastakoti, Yusuke Yamauchi, Zongwen LiuAbstract:A hybrid mesoporous TiO2/Zn2Ti3O8 film with a pore size of around 40 nm is successfully synthesized by the Polymeric Micelle assembly approach. The chemically distinct units of Polymeric Micelles of the poly(styrene–2-vinylpyridine–ethylene oxide) triblock copolymer simultaneously contribute to the formation of mesoporous TiO2/Zn2Ti3O8 films with enhanced photocatalytic activity during H2 evolution reaction.
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Polymeric Micelle assembly for the smart synthesis of mesoporous platinum nanospheres with tunable pore sizes
Angewandte Chemie, 2015Co-Authors: Yunqi Li, Bishnu Prasad Bastakoti, Victor Malgras, Cuiling Li, Jing Tang, Yusuke YamauchiAbstract:A facile method for the fabrication of well-dispersed mesoporous Pt nanospheres involves the use of a Polymeric Micelle assembly. A core–shell–corona type triblock copolymer [poly(styrene-b-2-vinylpyridine-b-ethylene oxide), PS-b-P2VP-b-PEO] is employed as the pore-directing agent. Negatively charged PtCl42− ions preferably interact with the protonated P2VP+ blocks while the free PEO chains prevent the aggregation of the Pt nanospheres. The size of the mesopores can be finely tuned by varying the length of the PS chain. Furthermore, it is demonstrated that the metallic mesoporous nanospheres thus obtained are promising candidates for applications in electrochemistry.
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synthesis of mesoporous tio2 sio2 hybrid films as an efficient photocatalyst by Polymeric Micelle assembly
Science & Engineering Faculty, 2014Co-Authors: Bishnu Prasad Bastakoti, Yusuke Yamauchi, Yunqi Li, Masataka Imura, Soo Min HwangAbstract:Thermally stable mesoporous TiO2/SiO2 hybrid films with pore size of 50 nm have been synthesized by adopting the Polymeric Micelle-assembly method. A triblock copolymer, poly(styrene-b-2-vinyl pyridine-b-ethylene oxide), which serves as a template for the mesopores, was utilized to form Polymeric Micelles. The effective interaction of titanium tetraisopropoxide (TTIP) and tetraethyl orthosilicate (TEOS) with the Polymeric Micelles enabled us to fabricate stable mesoporous films. By changing the molar ratio of TEOS and TTIP, several mesoporous TiO2/SiO2 hybrid films with different compositions can be synthesized. The presence of amorphous SiO2 phase effectively retards the growth of anatase TiO2 crystal in the pore walls and retains the original mesoporous structure, even at higher temperature (650 °C). These TiO2/SiO2 hybrid films are of very high quality, without any cracks or voids. The addition of SiO2 phase to mesoporous TiO2 films not only adsorbs more organic dyes, but also significantly enhances the photocatalytic activity compared to mesoporous pure TiO2 film without SiO2 phase.
Teruo Okano - One of the best experts on this subject based on the ideXlab platform.
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a novel synthetic tissue adhesive hydrogel using a crosslinkable Polymeric Micelle
Journal of Biomedical Materials Research Part A, 2007Co-Authors: Yoshihiko Murakami, Masayuki Yokoyama, Teruo Okano, H Nishida, Yasuko Tomizawa, Masahiro Endo, Hiromi KurosawaAbstract:We prepared a novel tissue-adhesive hydrogel by using a Polymeric Micelle consisting of an aldehyde-terminated poly(ethylene glycol)–poly(D,L-lactide) (PEG–PLA) block polymer. A Schiff base is chemically formed between the amino groups in a polyallylamine and the aldehyde groups on the surface of Polymeric Micelles. The hydrogel was formed in ∼2 s when the Polymeric Micelle solution and polyallylamine solution are mixed in vitro. The hydrogel was rapidly formed in vivo, and it adhered to a tissue surface. Our novel tissue-adhesive hydrogel creates no risk of infectious contaminations, because it consists of only synthetic materials. Further, PEG and PLA are known to be biocompatible and noncytotoxic. The results obtained in the present study show that a hydrogel prepared by the formation of a Schiff base between aldehyde and amine groups will potentially address the need for novel tissue-adhesive materials. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
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a novel synthetic tissue adhesive hydrogel using a crosslinkable Polymeric Micelle
Journal of Biomedical Materials Research Part A, 2007Co-Authors: Yoshihiko Murakami, Masayuki Yokoyama, Teruo Okano, H Nishida, Yasuko Tomizawa, Masahiro Endo, Hiromi KurosawaAbstract:We prepared a novel tissue-adhesive hydrogel by using a Polymeric Micelle consisting of an aldehyde-terminated poly(ethylene glycol)–poly(D,L-lactide) (PEG–PLA) block polymer. A Schiff base is chemically formed between the amino groups in a polyallylamine and the aldehyde groups on the surface of Polymeric Micelles. The hydrogel was formed in ∼2 s when the Polymeric Micelle solution and polyallylamine solution are mixed in vitro. The hydrogel was rapidly formed in vivo, and it adhered to a tissue surface. Our novel tissue-adhesive hydrogel creates no risk of infectious contaminations, because it consists of only synthetic materials. Further, PEG and PLA are known to be biocompatible and noncytotoxic. The results obtained in the present study show that a hydrogel prepared by the formation of a Schiff base between aldehyde and amine groups will potentially address the need for novel tissue-adhesive materials. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
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A Polymeric Micelle MRI contrast agent with changeable relaxivity.
Journal of controlled release : official journal of the Controlled Release Society, 2006Co-Authors: Emiko Nakamura, Teruo Okano, Kimiko Makino, Tatsuhiro Yamamoto, Masayuki YokoyamaAbstract:Polymeric Micelles were formed from cationic polymers (polyallylamine or protamine) and anionic block copolymers (poly(ethylene glycol)-b-poly(aspartic acid) derivative) that bound Gd ions providing high contrasts in Magnetic Resonance Imaging (MRI) by shortening the T(1) longitudinal relaxation time of protons of water. The Gd-binding block copolymer alone showed high relaxivity (T(1)-shortening ability) values from 10 to 11 mol(-1) s(-1), while the Polymeric Micelles exhibited low relaxivity values from 2.1 to 3.6 mol(-1) s(-1). These findings point to the feasibility of a novel MRI contrast agent that selectively provides high contrasts at solid tumor sites owing to a dissociation of the Micelle structures, while selective delivery to the tumor sites is achieved in the Polymeric Micelle form.
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Intelligent thermoresponsive Polymeric Micelles for targeted drug delivery
Journal of Drug Delivery Science and Technology, 2006Co-Authors: Masamichi Nakayama, Teruo OkanoAbstract:Nano-order sized supramolecular assemblies called Polymeric Micelles possess two-separated phase structure; a hydrated hydrophilic outer shell provides their highly structural stabilities in aqueous media and a hydrophobic inner core acts as a drug loading container. First anticancer Polymeric Micelle carrier systems showed a selective accumulation at solid tumor tissues and a subsequent in vivo anticancer activity. Recently, stimuli-responsive Polymeric Micelles have been designed as the next generation of Micelle systems for application in selective drug release at target sites by physical and/or chemical signals. We suggested a concept using thermoresponsive Polymeric Micelle drug carriers in conjunction with local heating systems for multi-targeting therapeutic systems to achieve effective cancer chemotherapy with fewer side effects. The present review article mainly focuses on strategy and molecular design of thermoresponsive Polymeric Micelles and discusses their potential for an intelligent targeted drug carrier system with some examples containing anti-cancer drugs.
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polymer design and incorporation methods for Polymeric Micelle carrier system containing water insoluble anti cancer agent camptothecin
Journal of Drug Targeting, 2004Co-Authors: Masayuki Yokoyama, Teruo Okano, Kumi Kawano, Praneet Opanasopit, Yoshie MaitaniAbstract:A water-insoluble anti-cancer agent, camptothecin (CPT) was incorporated to a Polymeric Micelle carrier system forming from poly(ethylene glycol)-poly(aspartate) block copolymers. Incorporation efficiency and stability were analyzed in correlation with chemical structures of the inner core-forming hydrophobic blocks as well as with incorporation methods. Among three incorporation methods (dialysis, emulsion and evaporation methods), an evaporation method brought about much higher CPT yields with less aggregation than the other two methods. By the evaporation method, CPT was incorporated to Polymeric Micelles in considerably high yields and with high stability using block copolymers possessing high contents of benzyl and methylnaphtyl ester groups as hydrophobic moieties. This indicates importance of molecular design of the hydrophobic block chain to obtain targeting using Polymeric Micelle carriers as well as importance of the drug incorporation method.
Nobuhiro Nishiyama - One of the best experts on this subject based on the ideXlab platform.
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Polymeric Micelle platform for multimodal tomographic imaging to detect scirrhous gastric cancer
ACS Biomaterials Science & Engineering, 2015Co-Authors: Yutaka Miura, Horacio Cabral, Ichio Aoki, Atsushi B Tsuji, Aya Sugyo, Hitomi Sudo, Masayuki Inubushi, Masakazu Yashiro, Kosei Hirakawa, Nobuhiro NishiyamaAbstract:Scirrhous gastric cancer (SGC) is a recalcitrant tumor, which is among the most lethal cancers. A critical issue for the improvement of SGC prognosis is the lack of an effective imaging method for accurate detection and diagnosis. Because combined nuclear medicine imaging with magnetic resonance imaging (MRI) has the ability to detect cancer with high sensitivity, and quantitation and spatial resolution, it has potential to overcome the issues with SGC detection. Herein, we designed and synthesized a new block copolymer poly(ethylene glycol)-b-poly(γ-benzyl l-glutamate) linked with a chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-PEG-b-PBLG) to provide a platform for multimodal tomographic imaging. We then successfully prepared DOTA-functionalized Polymeric Micelles (DOTA/m) measuring 30 nm in diameter, which is an appropriate size to penetrate deeply into tumors with thick fibrosis, including SGC. 111In-labeled DOTA/m highly accumulated in Colon-26 tumors (mouse colon cancer with...
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three layered polyplex Micelle as a multifunctional nanocarrier platform for light induced systemic gene transfer
Nature Communications, 2014Co-Authors: Takahiro Nomoto, Nobuhiro Nishiyama, Kensuke Osada, Yu Matsumoto, Shigeto Fukushima, Michiaki Kumagai, Kaori Machitani, Kanjiro Miyata, Kazunori KataokaAbstract:Light-controlled mechanisms for the delivery of drug molecules to cells is a promising route for non-invasive disease therapy. Here, the authors develop a photosensitive Polymeric Micelle for light-induced gene transfection and show its effectiveness in vivo via systemic administration.
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in vivo antitumor activity of the folate conjugated ph sensitive Polymeric Micelle selectively releasing adriamycin in the intracellular acidic compartments
Bioconjugate Chemistry, 2007Co-Authors: Nobuhiro Nishiyama, Kazunori KataokaAbstract:Cancer treatment efficacy and safety of the environmentally sensitive Polymeric Micelle drug carriers were significantly increased by optimizing the number of ligands on their surface. These Micelles were designed to target the cancerous tumors through the interaction between folate and its receptors that overexpress on the cancer cell membrane while achieving pH-controlled drug release in the intracellular acidic compartments such as endosomes and lysosomes. In order to elucidate the effects of folate on cytotoxicity, biodistribution, anticancer activity, and pharmacological properties, folate concentration on the surface of the Micelles was controlled by precise synthesis of two different amphiphilic block copolymers that self-assemble into spherical Micelles, folate−poly(ethylene glycol)−poly(aspartate-hydrazone-adriamycin) with γ-carboxylic acid activated folate and methoxy-poly(ethylene glycol)−poly(aspartate-hydrazone-adriamycin) without folate. It is of significance that, although folate conjugatio...
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nanotechnology based photodynamic therapy for neovascular disease using a supramolecular nanocarrier loaded with a dendritic photosensitizer
Nano Letters, 2005Co-Authors: Ryuichi Ideta, Nobuhiro Nishiyama, Fumitaka Tasaka, Woo Dong Jang, Guodong Zhang, Atsushi Harada, Yasuo Yanagi, Yasuhiro Tamaki, Takuzo Aida, Kazunori KataokaAbstract:Photodynamic therapy (PDT) for exudative age-related macular degeneration (AMD) was evaluated using a supramolecular nanomedical device, that is, a novel dendritic photosensitizer (DP) encapsulated by a Polymeric Micelle formulation. The characteristic dendritic structure of the DP prevents aggregation of its core sensitizer, thereby inducing a highly effective photochemical reaction. With its highly selective accumulation on choroidal neovascularization (CNV) lesions, this treatment resulted in a remarkably efficacious CNV occlusion with minimal unfavorable phototoxicity.
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preparation and biological characterization of Polymeric Micelle drug carriers with intracellular ph triggered drug release property tumor permeability controlled subcellular drug distribution and enhanced in vivo antitumor efficacy
Bioconjugate Chemistry, 2005Co-Authors: Nobuhiro Nishiyama, Shigeto Fukushima, Hiroyuki Koyama, Matsumura Yasuhiro, Kazunori KataokaAbstract:A novel intracellular pH-sensitive Polymeric Micelle drug carrier that controls the systemic, local, and subcellular distributions of pharmacologically active drugs has been developed in this study. The Micelles were prepared from self-assembling amphiphilic block copolymers, poly(ethylene glycol)-poly(aspartate hydrazone adriamycin), in which the anticancer drug, adriamycin, was conjugated to the hydrophobic segments through acid-sensitive hydrazone linkers. By this polymer design, the Micelles can stably preserve drugs under physiological conditions (pH 7.4) and selectively release them by sensing the intracellular pH decrease in endosomes and lysosomes (pH 5−6). In vitro and in vivo studies show that the Micelles have the characteristic properties, such as an intracellular pH-triggered drug release capability, tumor-infiltrating permeability, and effective antitumor activity with extremely low toxicity. The acquired experimental data clearly elucidate that the optimization of both the functional and st...