Hiroyuki Koide's research while affiliated with University of Shizuoka and other places

Publications (52)

Article
Homeostasis can be achieved by adding a protein supplement; however, an appropriate vector is required to deliver the protein into the cell because of the low stability of proteins in the blood and low cell membrane permeability. Here we report an easy one-step method of encapsulating proteins into liposomes for delivery. We used negatively charged...
Article
Full-text available
Sepsis is a life-threatening condition caused by the extreme release of inflammatory mediators into the blood in response to infection (e.g., bacterial infection, COVID-19), resulting in the dysfunction of multiple organs. Currently, there is no direct treatment for sepsis. Here we report an abiotic hydrogel nanoparticle (HNP) as a potential therap...
Article
Protein affinity reagents that specifically and strongly bind to target molecules are widely used in disease detection, diagnosis, and therapy. Although antibodies and their fragments are the gold standard in protein-protein inhibitors (PPIs), synthetic polymers such as linear polymers, dendrimers, and nanoparticles as cost-effective PPIs have attr...
Article
Macromolecular toxins often induce inflammatory cytokine production, multiple-organ dysfunction, and cell death. Synthetic polymer ligands (PLs) prepared with several functional monomers have the potential of neutralizing target toxins after binding to them; therefore, they are of significant interest as abiotic antidotes. Although PLs show little...
Article
Synthetic polymers prepared using several functional monomers have attracted attention as cost-effective protein affinity reagents and alternative to antibodies. We previously reported the synthesis of poly NIPAm-based nanoparticles (NPs) using several functional monomers that can capture target molecules. In this study, we designed NPs for capturi...
Article
Protein–protein (e.g., antibody–antigen) interactions comprise multiple weak interactions. We have previously reported that lipid nanoparticles (LNPs) bind to and neutralize target toxic peptides after multifunctionalization of the LNP surface (MF-LNPs) with amino acid derivatives that induce weak interactions; however, the MF-LNPs aggregated after...
Chapter
Small interfering RNA (siRNA) is a novel therapeutic modality for the treatment of intractable diseases; however, the development of a useful siRNA delivery vector is imperative for clinical use. Since siRNA works in the cytoplasm, the ability of the carrier to escape destruction in the endosomes is a highly required characteristic for the inductio...
Preprint
Full-text available
Sepsis is a life-threatening condition caused by the extreme release of inflammatory mediators into the blood in response to infection (e.g., bacterial infection, COVID-19), resulting in the dysfunction of multiple organs. Currently, there is no direct treatment for sepsis. Here we report an abiotic hydrogel nanoparticle (HNP) as a potential therap...
Article
Full-text available
Protein affinity reagents (e.g., antibodies) are often used for basic research, diagnostics, separations, and disease therapy. Although a lot of “synthetic” protein affinity reagents have been developed as a cost‐effective alternative to antibodies, their low biocompatibility is a considerable problem for clinical application. Lipid nanoparticles (...
Article
Multifunctional synthetic polymers can bind to target molecules and are therefore widely investigated in diagnostics, drug delivery carriers, and separation carriers. Because these polymers are synthesized from nonbiological components, purification processes (e.g., chromatography, dialysis, extraction, and centrifugation) must be conducted after t...
Article
Protein affinity reagents are widely used for basic research, diagnostics, and disease therapy. Antibodies and their fragments are known as the most common protein affinity reagents. They specifically and strongly bind to target molecules and inhibit their functions. Thus, antibody drugs have increased in the recent two decades for disease therapy,...
Article
Small interfering RNA (siRNA) has been expected to be a unique pharmaceutic for the treatment of broad-spectrum intractable diseases. However, its unfavorable properties such as easy degradation in the blood and negative-charge density are still a formidable barrier for clinical use. For disruption of this barrier, siRNA delivery technology has bee...
Article
RNA interference induced by small interfering RNA (siRNA) is a promising strategy for the treatment of various intractable diseases including cancer. Lipid nanoparticles (LNP) composed of ionizable lipids and siRNA are known as a leading siRNA delivery system. However, LNPs composed of conventional ionizable lipids will be aggregated in the physiol...
Article
The affinity of a synthetic polymer nanoparticle (NP) to a target biomacromolecule is determined by the association and dissociation rate constants (kon, koff) of the interaction. The individual rates and their sensitivity to local environmental influences are important factors for the on demand capture and release a target biomacromolecule. Positi...
Article
Although N-methyl-d-aspartate receptor (NMDAR) antagonists are hopeful therapeutic agents against cerebral ischemia/reperfusion (I/R) injury, effective approaches are needed to allow such agents to pass through the blood-brain barrier (BBB), thus increasing bioavailability of the antagonists to realize secure treatment. We previously demonstrated t...
Article
Lipid-based nanoparticles, a potential nonviral vector due to their good biocompatibility and biodegradability, have been extensively developed for the delivery of small interfering RNA (siRNA). We designed a unique pH-responsive lipid derivative, a dioleylphosphate-diethylenetriamine conjugate (DOP-DETA). DOP-DETA consists of a pH-responsive triam...
Article
Full-text available
Type 2 diabetes mellitus (T2DM) is characterized by persistent hyperglycemia and is influenced by genetic and environmental factors. Optimum T2DM management involves early diagnosis and effective glucose-lowering therapies. Further research is warranted to improve our understanding of T2DM pathophysiology and reveal potential roles of genetic predi...
Article
A small interfering RNA (siRNA) delivery system using dioleylphosphate–diethylenetriamine conjugate (DOP-DETA)-based liposomes (DL) was assessed for systemic delivery of siRNA to tumors. DL carrying siRNA capable of inducing efficient gene silencing with low doses of siRNA were modified with polyethylene glycol (PEG-DL/siRNA) for systemic injection...
Article
Synthetic polymers are of interest as stable and cost-effective biomolecule-affinity reagents, since these polymers interact with target biomolecules both in vitro and in the bloodstream. However, little has been reported about orally administered polymers capable of capturing a target molecule and inhibiting its intestinal absorption. Here, we des...
Article
While the influence of pKa provided by amine-containing materials in siRNA delivery vectors for use in gene-silencing has been widely studied, there are little reports in which amine pKa is controlled rigorously by using bioisosteres and its effect on gene-silencing. Here, we report that amine pKa could be rigorously controlled by replacement of hy...
Article
Protein affinity reagents (PARs), frequently antibodies, are essential tools for basic research, diagnostics, separations and for clinical applications. However, there is growing concern about the reproducibility, quality and cost of recombinant and animal-derived antibodies. This has prompted the development of alternatives that could offer econom...
Article
Triple-negative breast cancer is one of intractable cancers that are not sensitive to the treatment with existing molecular-targeted drugs. Recently, there has been much interest in RNA interference-mediated treatment of triple-negative breast cancer. In the present study, we have developed lipid nanoparticles encapsulating siRNA (LNP-siRNA) decora...
Article
Many of macromolecular toxins induce cell death by directly interacting with cells or induction of inflammatory cytokines. Abiotic polymer ligands (PLs) composed of functional monomers are able to bind and neutralize toxins in vivo and are of great interest for efficient antidotes. However, little has been reported about recognition and neutralizat...
Article
Protein affinity reagents are widely used in basic research, diagnostics and separations and for clinical applications, the most common of which are antibodies. However, they often suffer from high cost, and difficulties in their development, production and storage. Here we show that a synthetic polymer nanoparticle (NP) can be engineered to have m...
Article
For ischemic stroke treatment, extension of the therapeutic time window (TTW) of thrombolytic therapy with tissue plasminogen activator (tPA) and amelioration of secondary ischemia/reperfusion (I/R) injury are most desirable. Our previous studies have indicated that liposomal delivery of neuroprotectants into an ischemic region is effective for str...
Article
Bioluminescent imaging (BLI) has become a useful tool for monitoring bacterial infections in real time. Citrobacter rodentium and its BLI are widely used as a murine model of enteropathogenic and enterohaemorrhagic Escherichia coli infection. In this study, we evaluated the protective effects of the probiotic Lactobacillus brevis KB290 against C. r...
Article
Full-text available
The development of a diagnostic technology that can accurately determine the pathological progression of ischemic stroke and evaluate the therapeutic effects of cerebroprotective agents has been desired. We previously developed a novel PET probe, 2-tert-butyl-4-chloro-5-{6-[2-(2-18F-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([18...
Article
Fasudil, a Rho-kinase inhibitor, is a promising neuroprotectant against ischemic stroke; however, its low bioavailability is an obstacle to be overcome. Our previous study revealed that the liposomal drug delivery system is a hopeful strategy to increase the therapeutic efficacy of neuroprotectants. In the present study, the usefulness of intraveno...
Article
Small interfering RNA (siRNA) has the potential to be a candidate as a cure for intractable diseases. However, an appropriate vector is required for siRNA delivery because of the low transfection efficiency of siRNA without a vector and its easy degradation in vivo. Here, we report a simple, only one step, and efficient method for siRNA encapsulati...
Article
Synthetic polymer nanoparticles (NPs) with intrinsic affinity for target biomacromolecules hold great promise in the development of novel tools for biological and biomedical research. We recently reported the design and synthesis of abiotic, synthetic polymer NPs with high intrinsic affinity for a peptide toxin melittin. The NP was selected by scre...
Article
PTEN-positive tumors are not susceptible to the treatment with rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR). Here, we determined the susceptibility of PTEN-positive cells to small interfering RNA for mTOR (si-mTOR) by using a novel liposomal delivery system. For this purpose, we prepared dicetyl phosphate-tetraethylenepentami...
Article
Previously, we developed tetraethylenepentamine-based polycation liposomes (TEPA-PCL) as a vector for the delivery of small RNAs. In the present research, we attempted tumor-targeted delivery of miR-499 via systemic administration and evaluated the potency of this system as a therapeutic strategy to treat cancer. Lipoplexes were formed by mixing ch...
Article
In the development of nucleic acid medicines such as small interfering RNA (siRNA) drugs, one problem is how to study the pharmacokinetics and pharmacodynamics, since the precise in vivo behavior of siRNA is hard to detect. In this research, to establish a highly sensitive detection system of siRNA biodistribution in the whole body, the technology...
Article
We previously observed that rhinacanthins, which are the main naphthoquinone esters isolated from the roots of a Thai medicinal plant, Rhinacanthus nasutus KURZ. (family Acanthaceae), suppress the growth of Meth-A sarcoma in the tumor-bearing mice and that rhinacanthin-N has the strongest antitumor activity among these naphthoquinone esters tested....
Article
An accelerated blood clearance (ABC) phenomenon is induced by repeated injections of poly(ethylene glycol)-modified (PEGylated) liposomes. We previously indicated that the phenomenon was induced by polymeric micelles possessing PEG chains like as liposomes, although, the induction mechanism of the ABC phenomenon is not fully elucidated. In the pres...
Article
Full-text available
Synthetic polymer nanoparticles (NPs) that bind venomous molecules and neutralize their function in vivo are of significant interest as "plastic antidotes." Recently, procedures to synthesize polymer NPs with affinity for target peptides have been reported. However, the performance of synthetic materials in vivo is a far greater challenge. Particle...
Article
Previously we developed dicetyl phosphate-tetraethylenepentamine-based polycation liposomes (TEPA-PCL) for use in small interfering RNA (siRNA) therapy. In the present study, mammalian target of rapamycin (mTOR) expression in cancer cells was silenced with mTOR-siRNA (simTOR) formulated in TEPA-PCL modified with Ala-Pro-Arg-Pro-Gly (APRPG), a pepti...
Article
Full-text available
A practical synthesis of nobiletin, a polymethoxylated citrus flavone, was accomplished by utilizing our novel flavone synthesis. Synthetic nobiletin was labelled by selective demethylation and rapid incorporation of (11)C atom. Positron emission tomography images successfully visualized the brain distribution, which may provide therapeutic benefit...
Article
Dicetyl phosphate-tetraethylenepentamine (DCP-TEPA) conjugate was newly synthesized and formed into liposomes for efficient siRNA delivery. Formulation of DCP-TEPA-based polycation liposomes (TEPA-PCL) complexed with siRNA was examined by performing knockdown experiments using stable EGFP-transfected HT1080 human fibrosarcoma cells and siRNA for GF...
Article
We report that simple, synthetic organic polymer nanoparticles (NPs) can capture and clear a target peptide toxin in the bloodstream of living mice. The protein-sized polymer nanoparticles, with a binding affinity and selectivity comparable to those of natural antibodies, were prepared by combining a functional monomer optimization strategy with mo...
Article
Pharmacokinetic study of small interfering RNA (siRNA) is an important issue for the development of siRNAs for use as a medicine. For this purpose, a novel and favorable positron emitter-labeled siRNA was prepared by amino group-modification using N-succinimidyl 4-[fluorine-18] fluorobenzoate ([(18)F]SFB), and real-time analysis of siRNA traffickin...
Article
Repeated injection of polyethyleneglycol-modified (PEGylated) liposomes causes a rapid clearance of them from the bloodstream, this phenomenon is called accelerated blood clearance (ABC). In the present study, we focused on the immune system responsible for the ABC phenomenon. PEGylated liposomes were preadministered to BALB/c mice and [(3)H]-label...
Article
Liposomes modified with polyethylene glycol (PEG) can stably exist in the bloodstream because the PEG on the liposomes attracts a water shell to the liposomal surface. Since these liposomes are long circulating nanocarriers, they are used as drug and gene delivery tools. Repeat injection of PEGylated liposomes, however, is known to induce the accel...
Article
Designed polymer nanoparticles (NPs) capable of binding and neutralizing a biomacromolecular toxin are prepared. A library of copolymer NPs is synthesized from combinations of functional monomers. The binding capacity and affinity of the NPs are individually analyzed. NPs with optimized composition are capable of neutralizing the toxin even in a co...
Article
Positron emission tomography (PET) is a noninvasive imaging technology that enables the determination of biodistribution of positron emitter-labeled compounds. Lipidic nanoparticles are useful for drug delivery system (DDS), including the artificial oxygen carriers. However, there has been no appropriate method to label preformulated DDS drugs by p...
Article
A repeat-injection of polyethylene glycol-modified liposomes (PEGylated liposomes) causes a rapid clearance of them from the blood circulation in certain cases that is referred to as the accelerated blood clearance (ABC) phenomenon. In the present study, we examined whether polymeric micelles trigger ABC phenomenon or not. As a preconditioning trea...
Article
To investigate chemopreventive effect of liposomal beta-sitosterol on tumor metastasis, we prepared liposomal beta-sitosterol composed of egg yolk phosphatidylcholine for oral delivery. Although orally administered beta-sitosterol (4 micromol as beta-sitosterol/mouse) was not absorbed into plasma, the amount of immune response cytokines such as IL-...
Article
To investigate chemopreventive effect of liposomal β-sitosterol on tumor metastasis, we prepared liposomal β-sitosterol composed of egg yolk phosphatidylcholine for oral delivery. Although orally administered β-sitosterol (4 μmol as β-sitosterol/mouse) was not absorbed into plasma, the amount of immune response cytokines such as IL-12 and IL-18 was...
Article
OK-432 (Picibanil), a Streptococcal immunotherapeutic agent, has been used for immunotherapy of various cancers as a biological response modifier (BRM). However, OK-432 contains multiple components consisting of immunotherapeutic ones and contaminants which may weaken the effects or exert side-effects. In this study, we investigated extraction of c...

Citations

... Organic nanoparticles, such as polymer-, lipid-and carbon-based nanoparticles, and inorganic nanoparticles, like gold and magnetic nanoparticles, have been broadly explored for possible clinical purposes. In particular, multifunctional synthetic polymers and lipid-based nanoparticles such as poly (lactide-co-glycolide) (PLGA) nanoparticles, liposomes, melanoidins, and dendrimers generated interest as an abiotic protein affinity reagent for therapeutic use, cell engineering, and drug delivery carrier [43]. ...
... It should be noted that in the case of nucleic acid delivery (e.g., siRNA and antisense oligonucleotides), the efficiency of endosomal escape is generally estimated to be less than a few percent 36 . Even under treatment conditions yielding the desired cell activity, CLSM analysis of fluorescently labeled nucleic acids often yield punctate cell distribution without spreading throughout the cell, indicating that the majorities of the nucleic acids are trapped in endosomes or form aggregate in cytosol [37][38][39] . The spread cytosolic signals of NLS-(− 30)GFP observed in this study thus support the suitability of the DOP-DEDA-based LNP system for intracellular protein delivery. ...
... They suggested that MLT nanoliposomes perform better in HCC therapy due to remarkable antitumor properties [131]. In studies on MLT-loaded PEGylated lipid-NPs, prolonged circulation in the blood and lower aggregation ability have been observed [132]. A study by Peng et al. demonstrated that multiple-arm PEGylation of MLT decreased the hemolytic effects and altered the coagulation profiles of MLT [129]. ...
... However, these negatively charged molecules are highly unstable under physiological conditions and are poorly taken up by cells. For this reason, many nanomedicines, in particular, cationic and especially ionizable lipid-based particles, have emerged to deliver nucleic acids [71]. In the area of NB, MXD3 was identified as a highly expressed oncogene in cell lines and primary tumors [68]. ...
... 9 Meanwhile, Plk-1 was identified to be overexpressed in many cancers and related to the tumor proliferation and migration. [10][11][12] Thus, Plk-1 could be used as a potential candidate for the development of anticancer drugs, and down-regulating the Plk-1 expression has been accepted as an effective route to achieve the tumor gene therapy. 13 For the use of siRNA as therapeutic drugs, there are many obstacles to be overcome, including the degradation by endogenous RNases, immunogenicity, short half-life, and limited cellular uptake. ...
... In addition, the efficacy of delivery is related to the strong affinity of endosomes and the weak affinity of cytoplasm for siRNA [192]. Encapsulating micellar NPs (MNPs) with palmitic-acid-linked siRNA (siRNA-PA) can enhance the efficacy of siRNA [193]. ...
... To disturb this signaling, Wang et al. developed a transferrin receptor targeting peptide-modified PEG-Lip encapsulating the neuroprotectant ZL006 (5-(3, 5-dichloro-2hydroxybenzylamino)-2-hydroxybenzoic acid), which selectively inhibits NMDAR activity and prevents glutamate-induced excitotoxicity [36]. Kikuchi et al. reported the use of liposomes encapsulating the NMDAR antagonist ifenprodil, which can be efficiently loaded into liposomes using a pH gradient between internal and external water phases [37]. Both liposomal neuroprotective agents targeting NMDAR signaling exhibited superior therapeutic effects on cerebral I/R injury compared to free drugs in t-MCAO rats. ...
... pKa value of 6.2 to 6.5 is required for gene silencing which leads to an inference that cationizing the ionizing lipid in a weakly acidic atmosphere serves to be critical in the delivery of siRNA and endosomal escape of the lipids can be reduced. [29] As the surface of the lipid becomes cationic, it facilitates nonspecific adsorption of serum proteins onto the surface of the lipids which occurs to a lesser extent in a neutral lipid surface normally. This can cause phagocytosis in the liver and also in the bloodstream reducing the efficiency of siRNA delivery. ...
... Pengaplikasian model DMT2 pada zebrafish yang paling umum yaitu dilakukan dengan metode diet tinggi lemak atau kelebihan nutrisi, pencelupan glukosa dan pemberian streptozotocin [48,49] sebagaimana pada tabel 4. ...
... Thus, suppression of nanoparticle aggregation in the blood contributes to prolonging the blood circulation period of nanoparticles, which allows for an increase in their therapeutic efficacy. For example, the abovementioned PEG modification has been reported to be useful for preventing nanoparticle aggregation by serum proteins [87,88]. Furthermore, the application of nanoparticles, particularly liposomes, can protect encapsulated drugs, such as small molecular hydrophilic/hydrophobic drugs, peptides, and proteins (e.g., t-PA and SOD), against enzymatic metabolism and degradation, resulting in enhancement of their therapeutic efficacy in target sites. ...