Comparison of thermosensitive properties of poly(amidoamine) dendrimers with peripheral N-isopropylamide groups and linear polymers with the same groups.
Explore the source record for details and available documents.
Journal Article↗
Biomedical subjects
Kenji Kono
Publications and source records attributed to Kenji Kono.
Overexpression of manganese superoxide dismutase by N-acetylcysteine in hyperoxic lung injury.
BACKGROUND: Exposure of animals to hyperoxia causes lung injury, characterized by diffuse alveolar damage and exudation of plasma into the alveolar space. Reactive oxygen species (ROS) play an important role in the development of hyperoxic lung injury. Mitochondrial oxidative phosphorylation is one of the major sources of ROS. N-acetylcysteine (NAC) is a precursor of glutathione (GSH), which functions as an antioxidant by reducing hydrogen peroxide to water and alcohols. NAC has been shown to diminish lung injury in a large variety of animal models. AIM: We elucidated the mechanism underlying the protective effects of NAC in hyperoxia-induced lung injury. METHODS: Male BALB/c mice were exposed to 98% oxygen for 72 h. The mice inhaled NAC or saline twice a day from 72 h before oxygen exposure to the end of experiment. RESULTS: Inhaled NAC increased the GSH level in lung homogenate. NAC also attenuated cellular infiltrations in both bronchoalveolar lavage fluid (BALF) and lung tissue. The total protein level in BALF and the level of 8-isoprostane, a marker of lipid peroxidation, in lung homogenate were decreased by inhalation of NAC. Inhaled NAC induced the overexpression of Mn superoxide dismutase (MnSOD) mRNA and protein, but did not alter the expressions of other antioxidant enzymes, including CuZnSOD, extracellular SOD, and glutathione peroxydase 1. CONCLUSION: These findings suggest that the antioxidant properties of NAC in hyperoxic lung injury involve a decrease in mitochondrial ROS in association with the induction of MnSOD, in addition to its role as a precursor of GSH.
Acetylcysteine↗
Enhancement of transfection activity of lipoplexes by complexation with transferrin-bearing fusogenic polymer-modified liposomes.
We previously developed complexes of lipoplexes containing 3beta-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol (DC-chol) and succinylated poly(glycidol)-modified liposome, which becomes fusogenic under weakly acidic condition, for use as a novel gene delivery system. This study explored the effect of lipoplex structures--the type of cationic lipid and cationic lipid/DNA charge ratio--on the transfection activity of those complexes. Three types of cationic lipid with different polar groups were used for the preparation of lipoplexes: DC-chol, N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methylsulfate (DOTAP), and 3,5-dipentadecyloxybenzamidine (TRX-20) with dimethylamino group, trimethylammonium group, and benzamidine group, respectively. Complexation with the SucPG-modified transferrin-bearing liposomes affected transfection activity of these lipoplexes differently. The TRX-20 lipoplexes exhibited the most marked enhancement of transfection activity upon complexation with the SucPG-modified liposomes among these lipoplexes. The cationic lipid/DNA charge ratio of the lipoplex and the amount of the transferrin-bearing SucPG-modified liposomes associated to the lipoplex also affected the transfection activity of the resultant complexes. Highly potent gene vectors were obtained by adjusting these factors.
Genetic Vectors↗
Thermosensitive properties of poly(amidoamine) dendrimers with peripheral phenylalanine residues.
Dendrimers are unique polymers with globular shapes and well-defined structures. We previously prepared poly(amidoamine) (PAMAM) dendrimers having phenylalanine (Phe) residues at every chain end of the dendrimer as efficient gene carriers. In this study, we found that Phe-derivatized PAMAM dendrimers change their water solubility depending on temperature. The dendrimers were soluble in aqueous solutions at low temperatures, but they became water-insoluble at temperatures above a specific threshold, which is termed the lower critical solution temperature (LCST). Although the LCST of Phe-modified dendrimers decreased with increasing dendrimer generation, these dendrimers exhibited an LCST of 20-30 degrees C under physiological conditions. In addition, the LCST of the dendrimers was controlled by introducing isoleucine (Ile) residues at chain ends of dendrimers at varying ratios with respect to Phe residues. The PAMAM dendrimers are known to encapsulate various drug molecules. For these reasons, temperature-sensitive dendrimers might be useful as efficient drug carriers with controlled size and temperature-responsive properties.
Dendrimers↗
[Spinal cord metastases in lung cancer: a clinical review of four cases].
We report 4 cases of spinal cord metastases of lung cancer detected by MRI. Histologically, 3 of the 4 cases were small cell carcinoma and the other was adenocarcinoma. All 3 cases of small cell carcinoma had neoplastic meningitis. MRI taken in these cases showed the multiple nodules in the cauda equina, which were seeded from brain metastases. One of them had intramedullary spinal cord metastases, which appeared as enlargement of the spinal cord or nodules in the spinal cord on MRI. Leg paralysis and incontinence progressed in all cases. The other case of adenocarcinoma had epidural spinal cord compression due to spinal metastasis. In this case irradiation and corticosteroids relieved her leg and back pain. Spinal cord metastases should be considered as a differential diagnosis in patients with numbness, pain or weakness in the extremities.
Adenocarcinoma↗
[A case of sarcoidosis with diffuse pulmonary arteriovenous malformations].
A 27-year-old woman was admitted because of right dry eye and blurred vision. She was given a diagnosis of uveitis due to sarcoidosis. Chest X-ray film showed bilateral hilar lymphadenopathy and multiple nodules in both lungs. The nodules were considered to be associated with sarcoidosis. However chest CT demonstrated that the nodules were well-defined and connected with two vessels. We diagnosed diffuse pulmonary arteriovenous malformations (AVMs) by 3D-CT. In three of sixteen AVMs, the feeding vessels were more than 3 mm wide in diameter on pulmonary arteriography, and those were embolized by platinum coils. The embolotherapy of diffuse AVMs could not ameliorate the shunt fraction sufficiently, but should reduce the possibility of the catastrophic complication of brain abscess.
Adult↗
Rendering poly(amidoamine) or poly(propylenimine) dendrimers temperature sensitive.
The poly(amidoamine) dendrimers having terminal isobutyramide (IBAM) groups were prepared by the reaction of isobutyric acid and the amine-terminated poly(amidoamine) dendrimers with generations (G) of 2 to 5 by using a condensing agent, 1,3-dicyclohexylcarbodiimide. 1H and 13C NMR revealed that an IBAM group was attached to essentially every chain end of the dendrimers. While the IBAM-terminated G2 dendrimer was soluble in water, the IBAM-terminated G3, G4, and G5 dendrimers exhibited the lower critical solution temperatures (LCSTs) at 75, 61, and 43 degrees C, respectively. Because the density of the terminal IBAM groups in the periphery of the dendrimer progressively increases with increasing dendrimer generation, the interaction of the IBAM groups might take place more efficiently, resulting in a remarkable decrease in the LCST. In addition, attachment of IBAM groups to poly(propylenimine) dendrimers could give the temperature-sensitive property, indicating that this is an efficient method to render dendrimers temperature sensitive.
Journal Article↗
Accumulation of boron compounds to tumor with polyethylene-glycol binding liposome by using neutron capture autoradiography.
The cytotoxic effect of boron neutron capture therapy (BNCT) is due to a nuclear reaction between 10B and thermal neutrons. It is necessary to accumulate the 10B atoms to the tumor cells selectively for effective BNCT. In order to achieve an accurate measurement of 10B concentrations in the biological samples, we employed a technique of neutron capture autoradiography (NCAR) of the sliced whole-body samples of tumor bearing mice using CR-39 plastic track detectors. The CR-39 detectors attached with samples were exposed to thermal neutrons in the thermal column of the TRIGA II reactor at the Institute for Atomic Energy, Rikkyo University and thermal neutron facility of Paul Scherer Institute(PSI). We obtained NCAR images for mice injected intravenously by 10B-PEG liposome, 10B-transferrin-PEG liposome, or 10B-bare liposome. The 10B concentrations in the tumor tissue of mice were estimated by means of alpha-track density measurements. In this study, we can increase the accumulation of 10B atoms in the tumor tissues by binding polyethylene-glycol chains to the surface of liposome, which increase the retention in the blood flow and escape the phagocytosis by reticulo-endothelial systems. Therefore, we will be able to apply NCAR technique for selection of effective 10B carrier in BNCT for cancer.
Animals↗
Temperature-sensitive liposomes.
Explore the source record for details and available documents.
1,2-Dipalmitoylphosphatidylcholine↗
[Six cases of thymic carcinoma: a clinical review].
Thymic carcinoma is rarer than thymoma and carries a very poor prognosis. No standard treatment has yet been established. Chemotherapy and radiation therapy are usually given to patients in whom surgery is not indicated. We clinically review six patients with thymic carcinoma (three men and three women) who were admitted to our hospital from 1992 through 2002. Their ages ranged from 56 to 81 years (median 70.5). Four patients had chest pain, two were unable to swallow, and in one, who was asymptomatic, the tumor was detected by chance. Histologically, five cases were squamous cell carcinomas, and one was a lymphoepithelioma-like carcinoma. Four of the six patients had distant metastasis at diagnosis. Only one patient was able to undergo surgery, two received radiation therapy alone, and three were administered chemoradiation. The response to the chemoradiation was progression of the disease in two patients and no change in one. The response to radiation therapy was partial response in one patient and no change in one. In summary, chest pain is the most common symptom of thymic carcinoma. A symptomatic case suggests a poor prognosis resulting from the clinical behavior of thymic carcinoma, such as early distant metastasis or direct invasion of surrounding organs. Histologically, squamous cell carcinoma is the most common, and thymic carcinoma appears to be generally resistant to chemotherapy and radiotherapy.
Aged↗
Fusogenic polymer-modified liposomes for the delivery of genes and charged fluorophores.
Explore the source record for details and available documents.
Epoxy Compounds↗
A case of Pasteurella haemolytica sepsis in a patient with mitral valve disease who developed a splenic abscess.
We report a patient with sepsis caused by Pasteurella haemolytica, an extremely rare etiologic agent of human infection, who had mitral valve disease and developed a splenic abscess.
Abscess↗
[Hospital infection with methicillin-resistant Staphylococcus aureus (MRSA)].
Explore the source record for details and available documents.
Cross Infection↗
Targetability and intracellular delivery of anti-BCG antibody-modified, pH-sensitive fusogenic immunoliposomes to tumor cells.
We prepared tumor-specific immunoliposomes by coupling anti-BCG monoclonal antibodies to pH-sensitive fusogenic liposomes modified with succinylated polyglycidol (sucPG), in order to obtain efficient binding to, and endocytotic internalization into, the tumor cells. Mouse colon carcinoma 26 cells, which are known to share a common antigen with BCG, were used in in vitro experiments. BCG-sucPG immunoliposomes showed fusion ability under acidic conditions. Fluorescence microscopic observation indicated that BCG-sucPG immunoliposomes bound to colon 26 tumor cells and induced receptor-mediated endocytosis at 37 degrees C. Fusion assay by resonance energy transfer using N-(7-nitro-2-1,3-benzoxadiazol-4-yl) diacyl phosphatidylethanolamine and N-(lissamine rhodamine B sulfonyl) diacyl phosphatidylethanolamine suggested that fusion between BCG-sucPG immunoliposomes and endosomal and/or lysozomal membrane did occur. These results imply that the BCG-sucPG immunoliposomes transfer their content into the cytoplasm by fusing with the endosomal and/or lysozomal membrane after recognition of target cells and subsequent internalization into the cells by endocytosis.
Animals↗
Effect of poly(ethylene glycol) grafts on temperature-sensitivity of thermosensitive polymer-modified liposomes.
A copolymer of N-isopropylacrylamide and N-acryloylpyrrolidine, which exhibits a lower critical solution temperature (LCST) at 38 degrees C, having a didodecyl group at the chain terminal was synthesized and calcein-loaded liposomes were prepared from a mixture of dioleoylphosphatidylethanolamine and the copolymer. While the contents release from the copolymer-modified liposomes was strongly accelerated around the LCST of the copolymer, some extent of the release was also observed below the LCST, probably because the partly-dehydrated copolymer chains interacted with the liposome membrane. When poly(ethylene glycol) with the number average molecular weight of 550 having a didodecyl group at the chain end was introduced into the copolymer-modified liposomes, the contents release from the copolymer-modified liposomes was effectively suppressed below the LCST but hardly affected above the LCST. As a result, the liposomes exhibited much sharper enhancement of the contents release in a narrow temperature region. The temperature-sensitive contents release property of the copolymer-modified liposomes became less significant in the presence of serum. However, inclusion of the anchor-bearing poly(ethylene glycol) derivative improved the contents release behavior of the copolymer-modified liposomes in the presence of serum.
Chemistry, Pharmaceutical↗
Synthesis of novel cationic lipids having polyamidoamine dendrons and their transfection activity.
We designed a novel type of cationic lipid, lipids with a cationic polar group in the polyamidoamine dendron, because these dendron-bearing lipids are expected to form complexes with plasmid DNA and achieve efficient transfection of cells by synergy of endosome buffering and membrane fusion with the endosome, both of which are useful for the promotion of the transfer of plasmid DNA from endosome to cytosol. Four kinds of lipids with polyamidoamine dendrons of first to fourth generations, DL-G1, DL-G2, DL-G3, and DL-G4, were synthesized. The lipid with a dendron of a higher generation exhibited greater ability to form lipoplexes with plasmid DNA, as estimated by agarose gel electrophoresis. While the DL-G1 lipoplex did not transfect CV1 cells, the lipoplexes containing the DL-G2, DL-G3, or DL-G4 could induce transfection of the cells, and their activity was elevated with increasing generation of the dendron. Addition of dioleoylphosphatidylethanolamine (DOPE), which is known to increase fusion ability of a lipid membrane, into the lipoplexes greatly enhanced their transfection activity. In addition, the comparison with DC-Chol-containing lipoplex, which is widely used as a nonviral vector, showed that the DL-G3-DOPE lipoplex exhibits more efficient transfections. These findings imply that these dendron-bearing lipids may form the basis for a novel family of cationic lipids for efficient gene delivery.
Animals↗
Temperature sensitization of liposomes by use of N-isopropylacrylamide copolymers with varying transition endotherms.
Three kinds of copolymers of N-isopropylacrylamide (NIPAM) with the same conformational transition temperature and varying transition endotherms were synthesized with N-acryloylpyrrolidine (APr), N,N-dimethylacrylamide (DMAM), and N-isopropylmethacrylamide (NIPMAM) as the comonomers. Two dodecyl groups were incorporated into the termini of these copolymers as an anchor for the fixation to a liposomal membrane. Egg yolk phosphatidylcholine liposomes having these copolymers were prepared and their temperature-sensitive contents release and association properties were investigated. While these copolymer exhibited a conformational transition at ca. 40 degrees C, DeltaH for the transition increased in the order of poly(APr-co-NIPAM) < poly(DMAM-co-NIPAM) < poly(NIPMAM-co-NIPAM). The liposomes containing poly(NIPMAM-co-NIPAM) showed a drastic release enhancement of entrapped calcein above the transition temperature, whereas the liposomes with poly(DMAM-co-NIPAM) and those with poly(APr-co-NIPAM) exhibited moderate and slight enhancement of calcein release above that temperature, respectively. On the contrary, the liposomes containing poly(APr-co-NIPAM) showed significant aggregation above the transition temperature, but the aggregation was hardly observed for the liposomes having poly(NIPMAM-co-NIPAM), indicating that poly(APr-co-NIPAM) more efficiently made the liposome surface hydrophobic. Thus, we concluded that the copolymer with a large DeltaH is suitable for obtaining functional liposomes with a temperature-sensitive contents release property, whereas the copolymer with a small DeltaH is appropriate for preparing functional liposomes with a temperature-sensitive surface property.
Acrylamides↗
Transfection activity of polyamidoamine dendrimers having hydrophobic amino acid residues in the periphery.
We designed poly(amidoamine) dendrimers with phenylalanine or leucine residues at their chain ends. Thereby, we achieved efficient gene transfection of cells through synergy of the proton sponge effect, which is induced by the internal tertiary amines of the dendrimer, and hydrophobic interaction by the hydrophobic amino acid residues in the dendrimer periphery. Dendrimers having 16, 29, 46, and 64 terminal phenylalanine residues were prepared by the reaction of the amine-terminated poly(amidoamine) G4 dendrimer and L-phenylalanine using condensing reagent 1,3-dicyclohexylcarbodiimide. Transfection activity of these phenylalanine-modified dendrimers for CV1 cells, an African green monkey kidney cell line, increased concomitant with the increasing number of the terminal phenylalanine residues, except for the dendrimer with 64 phenylalanine residues, which showed poor water solubility and hardly formed a complex with DNA at neutral pH. However, under weakly acidic conditions, the dendrimer with 64 phenylalanine residues formed a complex with DNA, thereby achieving highly efficient transfection. In contrast, the attachment of L-leucine residues was unable to improve the transfection activity of the parent dendrimer, probably because of the relatively lower hydrophobicity of this amino acid. The phenylalanine-modified dendrimer exhibited a higher transfection activity and a lower cytotoxicity than some widely used transfection reagents. For that reason, the phenylalanine-modified dendrimers are considered to be promising gene carriers.
Amino Acids↗