- Nanoparticle-Based Drug Delivery
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- Nanoplatforms for cancer theranostics
- Graphene and Nanomaterials Applications
- Bone Metabolism and Diseases
- DNA and Nucleic Acid Chemistry
- Dendrimers and Hyperbranched Polymers
- Alzheimer's disease research and treatments
- Cancer, Hypoxia, and Metabolism
- Hydrogen's biological and therapeutic effects
- Angiogenesis and VEGF in Cancer
- Silicone and Siloxane Chemistry
- Bone health and treatments
- Electron Spin Resonance Studies
- Characterization and Applications of Magnetic Nanoparticles
- Nanopore and Nanochannel Transport Studies
- Cell Adhesion Molecules Research
- Photodynamic Therapy Research Studies
- Tannin, Tannase and Anticancer Activities
- Synthesis and properties of polymers
- Biochemical effects in animals
- Protein Interaction Studies and Fluorescence Analysis
- Trace Elements in Health
- Nanoparticles: synthesis and applications
Innovation Center of NanoMedicine
2016-2025
Tokyo Medical and Dental University
2008-2024
Johns Hopkins Medicine
2024
Johns Hopkins University
2024
Universitat Internacional de Catalunya
2023
The University of Tokyo
2012-2016
Kyushu University
2004-2014
University of Tsukuba
2010-2011
Fukuoka Dental College
2008
Ligand-mediated drug delivery systems have enormous potential for improving the efficacy of cancer treatment. In particular, Arg-Gly-Asp peptides are promising ligand molecules targeting αvβ3/αvβ5 integrins, which overexpressed in angiogenic sites and tumors, such as intractable human glioblastoma (U87MG). We here achieved highly efficient to U87MG tumors by using a platinum anticancer drug-incorporating polymeric micelle (PM) with cyclic (cRGD) molecules. Intravital confocal laser scanning...
Osteoclasts are bone-resorbing, multinucleated giant cells that essential for bone remodeling and formed through cell fusion of mononuclear precursor cells. Although receptor activator nuclear factor–κB ligand (RANKL) has been demonstrated to be an important osteoclastogenic cytokine, the surface molecules involved in osteoclastogenesis mostly unknown. Here, we report seven-transmembrane receptor-like molecule, dendritic cell–specific transmembrane protein (DC-STAMP) is osteoclastogenesis....
Recently, nanocarriers that transport bioactive substances to a target site in the body have attracted considerable attention and undergone rapid progression terms of state art. However, few can enter brain via systemic route through blood-brain barrier (BBB) efficiently reach neurons. Here we prepare self-assembled supramolecular nanocarrier with surface featuring properly configured glucose. The BBB crossing accumulation this are boosted by glycaemic increase after fasting putative...
Polymeric nanoreactors (NRs) have distinct advantages to improve chemical reaction efficiency, but the in vivo applications are limited by lack of tissue-specificity. Herein, novel glucose oxidase (GOD)-loaded therapeutic vesicular NRs (theraNR) constructed based on a diblock copolymer containing poly(ethylene glycol) (PEG) and copolymerized phenylboronic ester or piperidine-functionalized methacrylate (P(PBEM-co-PEM)). Upon systemic injection, theraNR inactive normal tissues. At tumor site,...
Current antisense oligonucleotide (ASO) therapies for the treatment of central nervous system (CNS) disorders are performed through invasive administration, thereby placing a major burden on patients. To alleviate this burden, we herein report systemic ASO delivery to brain by crossing blood-brain barrier using glycemic control as an external trigger. Glucose-coated polymeric nanocarriers, which can be bound glucose transporter-1 expressed capillary endothelial cells, designed stable...
There are few reports on the physiological effects of metal nanoparticles (nps), especially with respect to their functions as scavengers for superoxide anion radical (O2(.-)) and hydroxyl (.OH). We tried detect scavenging activity Pt nps using a hypoxanthine-xanthine oxidase system O2(.-) Fenton UV/H2O2 .OH. Electron spin resonance analysis revealed that 2 nm particle size have ability scavenge The calculated rate constant O2(.-)-scavenging reaction was 5.03 +/- 0.03 x 10(7) M (-1) s (-1)....
Abstract The design and construction of nanoreactors are important for biomedical applications enzymes, but lipid‐ polymeric‐vesicle‐based have some practical limitations. We succeeded in preparing enzyme‐loaded polyion complex vesicles (PICsomes) through a facile protein‐loading method. preservation enzyme activity was confirmed even after cross‐linking the PICsomes. cross‐linked β‐galactosidase‐loaded PICsomes (β‐gal@PICsomes) selectively accumulated tumor tissue mice. Moreover, model...
Occult nodal metastases increase the risk of cancer recurrence, demoting prognosis and quality life patients. While targeted drug delivery by using systemically administered nanocarriers can potentially control metastatic disease, lymph node have been mainly dealt locally injecting nanocarriers, which may not always be applicable. Herein, we demonstrated that sub-50 nm polymeric micelles incorporating platinum anticancer drugs could target in a syngeneic melanoma model after systemic...
For systemic delivery of siRNA to solid tumors, a size-regulated and reversibly stabilized nanoarchitecture was constructed by using 20 kDa siRNA-loaded unimer polyion complex (uPIC) nm gold nanoparticle (AuNP). The uPIC selectively prepared charge-matched polyionic complexation poly(ethylene glycol)-b-poly(l-lysine) (PEG-PLL) copolymer bearing ∼40 positive charges (and thiol group at the ω-end) with single 40 negative charges. ω-end PEG-PLL further enabled successful conjugation uPICs onto...
Protein corona formation was regulated on the surface in vivo by molecular imprinting to enable polymeric nanogels acquire stealth upon intravenous administration. Albumin, most abundant protein blood, selected as a distinct component of for preparing molecularly imprinted (MIP-NGs) form an albumin-rich corona. Intravital fluorescence resonance energy transfer imaging rhodamine-labeled albumin and fluorescein-conjugated MIP-NGs showed that captured immediately after injection, forming...
Dexamethasone is a glucocorticoid steroid with anti-inflammatory properties used to treat many diseases, including cancer, in which it helps manage various side effects of chemo-, radio-, and immunotherapies. Here, we investigate the tumor microenvironment (TME)-normalizing dexamethasone metastatic murine breast cancer (BC). normalizes vessels extracellular matrix, thereby reducing interstitial fluid pressure, tissue stiffness, solid stress. In turn, penetration 13 32 nm dextrans, represent...
Current strategies to direct therapy-loaded nanoparticles the brain rely on functionalizing with ligands which bind target proteins associated blood-brain barrier (BBB). However, such have significant brain-specificity limitations, as are not exclusively expressed at microvasculature. Therefore, novel exploit alternative characteristics of BBB required overcome nonspecific nanoparticle targeting periphery, thereby increasing drug efficacy and reducing detrimental peripheral side effects....
Surface modification by poly(ethylene glycol) (PEG) onto gene carrier prepared through the electrostatic assembly of pDNA and polycation (polyplex) is a widely acknowledged strategy to advance their systemic application. In this regard, PEG crowdedness on polyplex surface should give important contribution in determining blood circulation property; however its accurate quantification has never been demonstrated. We report here first successful determination for PEGylated polyplexes (polyplex...
Nanomedicines capable of smart operation at the targeted site have potential to achieve utmost therapeutic benefits. Providing nanomedicines that respond endogenous stimuli with an additional external trigger may improve spatiotemporal control their functions, while avoiding drawbacks from inherent tissue distribution. Herein, by exploiting permeabilization endosomes induced photosensitizer agents upon light irradiation, we complemented intracellular action polymeric micelles incorporating...
Delivering therapeutic antibodies into the brain across blood–brain barrier at a level is promising while challenging approach in treatment of neurological disorders. Here, we present polymeric nanomicelle (PM) system capable delivering therapeutically effective levels 3D6 antibody fragments (3D6-Fab) parenchyma for inhibiting Aβ aggregation. PM assembly was achieved by charge-converting 3D6-Fab through pH-sensitive citraconylation to allow complexation with reductive-sensitive cationic...
Controlling the end-groups of biocompatible polymers is crucial for enabling polymer-based therapeutics and nanomedicine. Typically, end-group diversification a challenging time-consuming endeavor, especially prepared via ionic polymerization mechanisms with limited functional group tolerance. In this study, we present facile approach poly(2-oxazoline)s (POx), quick reliable production heterotelechelic to facilitate POxylation. The relies on careful tuning reaction parameters establish...
We describe the preparation of well-defined multicompartment micelles from polybutadiene-block-poly(1-methyl-2-vinyl pyridinium methyl sulfate)-block-poly(methacrylic acid) (BVqMAA) triblock terpolymers and their use as advanced drug delivery systems for photodynamic therapy (PDT). A porphyrazine derivative was incorporated into hydrophobic core during self-assembly served a model fluorescent probe at same time. The initial micellar corona is formed by negatively charged PMAA could be...